Real-Time Methods for Magnetic Resonance Spectra Acquisition, Imaging and Non-Invasive Ablation

ABSTRACT

The invention pertains to advances in real-time methods in nuclear magnetic resonance, magnetic resonance imaging, and non-invasive medical ablation by offering:
         a new real-time processing method for nuclear magnetic resonance (NMR) spectrum acquisition without external resonator(s), which remains stable despite magnetic field fluctuations,   a new processing method for nuclear magnetic resonance spectrum acquisition, which remains stable despite magnetic field fluctuations and resonator stability,   a new method of constructing predetermined magnets from appropriate magnetic material that allows for focusing the magnetic field in a target region,   a new dual frequency dynamic nuclear polarization (DNP) generator that polarizes the spin of electrons and acts as an NMR transmitter,   a new real-time processing method for visualizing, targeting, and guiding surgical and other non-invasive processes, and   a new method of non-invasive ablation, heat generation, and chemical reaction activation inside the human body to support a fully automatic or semi-automatic surgical procedure without the use of invasive devices, thus providing material reduction in risk to patient safety.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit under 35 U.S.C. § 119(e) of thepriority of the following U.S. Provisional Applications: U.S. 62/512,153filled on May 29, 2017, U.S. 62/545,014 filled on Aug. 14, 2017 and U.S.62/677,010 filled on May 27, 2018 by the present inventors.

TECHNICAL FIELD

This invention pertains to the field of nuclear magnetic resonance (NMR)spectroscopic and magnetic resonance imaging (MRI) techniques inreal-time chemical analysis, imaging diagnostics, and the development ofdevices for non-invasive heating and ablation with real-time guidanceand unsupervised and/or semi-supervised capabilities.

The invention proposed herein offers state-of-the-art non-invasivemethods to produce heat and/or accelerate chemical reactions in atargeted region situated in a large area (at least several times largerthan the targeted region). The intention of this patent application isto support the surgeon with a non-invasive heat blade/scalpel that isalso suitable for many other non-invasive, heat-generating and/orchemical reaction acceleration applications.

BACKGROUND OF THE INVENTION

The following is a tabulation of some prior art that presently appearsrelevant:

U.S. Patents Patent Number Kind Code Issue Date Patentee 8,035,388 B22011 Oct. 11 Casanova 8,148,988 B2 2012 Apr. 3 Blumich 2,545,994 A 1948Mar. 6 Gabler 3,676,791 A 1970 Mar. 17 Guenard 5,247,935 A 1992 Mar. 19Cline 2,993,638 A 1957 Jul. 24 Hall 4,415,959 A 1981 Mar. 20 Vinciarelli2,442,762 A 1943 Sep. 9 Ellis 1,862,559 A 1931 Aug. 14 White 4,075,042 A1973 Nov. 16 Das 4,342,608 A 1980 Apr. 21 Willens 5,867,026 A 1996 Apr.4 Haner 7,145,340 B2 2004 Nov. 4 Rindlisbacher 7,135,865 B2 2004 Mar. 22Park 6,396,274 B1 1999 Nov. 5 Commens 9,607,740 B2 2014 May 6 Rowe

U.S. Patent Application Publications Publication Nr. Kind Code Publ.Date Applicant 13397273 A1 2011 Feb. 22 Koseoglu 14394976 A1 2012 Apr.16 Hong 13164495 A1 2005 Oct. 27 Baker 12153349 A1 2007 May 21 Kitagawa

Foreign Patent Documents Foreign Doc. Nr. Cntry Code Kind Code Pub. DtApp or Patentee 001651 PCT A1 2009 Apr. 3 Prisner

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The following terms: finite difference methods, weighted differencemethods, pseudo-inverse matrix, least-squares minimization, totalleast-squares minimization, linear subspace methods, the conditionnumber of the matrix, low rank approximation, singular valuedecomposition (SVD), high performance liquid chromatography (HPLC),NOESY, and HSQC are well known nowadays and are clearly explained inWikipedia at http://www.wikipedia.org/.

All chemical elements are composed of one or more isotopes. Everyisotope is either a zero-spin isotope or a non-zero-spin isotope.

Nuclear magnetic resonance (NMR) is a physical phenomenon in whichnon-zero-spin isotopes absorb and re-emit electromagnetic radiation(energy) when placed in an external magnetic field.

NMR occurs at a specific resonance frequency; this frequency has alinear relationship with the strength of the permanent magnetic fieldand the magnetic properties of isotopes in the target field. Resonanceoccurs when the absorbed alternate magnetic field is transmittedorthogonally in the direction of the permanent magnetic field.

NMR spectrometers and magnetic resonance imaging (MRI) devices generallycomprise one or more magnets that produce a strong magnetic field withina test region. These magnets are usually superconducting magnets, thusNMR applications are restricted to laboratory environments. Currently,anisotropic permanent magnets, i.e. having all parts magnetized in onedirection, can achieve magnetic fields of only 1.5 T in strengthcompared to the 23 T of superconductor magnets. The NMR signal responsegrows quadratically with regard to the magnetic field strength used inthe experiment, which highly constrains the sensitivity andinformativity of spectra produced by NMR spectrometers and/or MRIdevices that have permanent magnets. NMR devices with permanent magnetsare often referred to as low-field NMR spectrometers.

When permanent magnets are combined with several other parts havingappropriate magnetization, it is possible to build a focused magneticfield of greater strength than the maximal field achievable with thepermanent magnet alone. One well-known combination is the Halbachstructure, introduced by Klaus Halbach in 1980, which makes a 5 Tmagnetic field possible with permanent magnets. This structure is oftenused in NMR spectrometers; however, it requires joining an enormousnumber of magnetized pieces. Doing so may be commercially ineffective,or unreasonably sophisticated when using magnets of small size.

The second problem characteristic of the Halbach structure is the highinstability of the generated magnetic field in terms of both time andtemperature if the same material is used throughout. U.S. Pat. No.8,148,988 describes a Halbach system that compensates for this drawbackthrough using several permanent magnets of different materials, albeitit only obtains almost half of the maximally achievable magnetic fieldstrength.

Halbach structures may be roughly classified as follows: 1D—linear,2D—cylindrical, and 3D—spherical. The maximal achievable magnetic fieldstrength for 1D structures—is 2B, for 2D—is B log(R_(o)/R_(i)), and for3D is (4/3)B log(R_(o)/R_(i)), where B is the maximum achievablemagnetic field for an anisotropic structure and R_(o) and R_(i) are theouter and inner radiuses of cylinders and/or spheres. This shows that 3Dstructures deliver the highest possible magnetic field: they aresuperior to 2D by a factor of 4/3, which increases sensitivity by almosta factor of 2!

At the same time, 3D structures require joining an enormous number ofmagnetized pieces, compared to 2D and 1D structures. They may be almostimpossible to build in the case of small-sized, portable magnets, orthey may not achieve the desired magnetic field because the process ofgluing and joining reduces magnetic field strength.

In addition, one of the biggest disadvantages of low-field NMRspectrometers is the high fluctuation of their magnetic fields. If themagnets are small (of a size appropriate to a portable device), theintensity and direction of the external magnetic field may be adverselyaffected. Even turning a 1.5 T NMR spectrometer to an angle about sixdegrees perpendicular to the Earth's magnetic force lines will ruin anymeasurements, and the device will have to be recalibrated. Even a slightmovement of the table on which a spectrometer is placed maysignificantly disturb the spectra generated. Another related difficultyis that currently available spectrometers usually require hightemperature stability (of the order of 0.01° C.), which is incompatiblewith chemical production equipment and in-situ measurements in chemicalreactions.

There are two well-known and widely-used primary approaches that improvethe sensitivity of NMR measurements: multi-nuclear and multi-dimensionalspectra acquisition and dynamic nuclear polarization (DNP).

The acquisition of multi-nuclear spectra usually requires one receivercoil for each type of nucleus and/or calibration of each spectrum tointernal standards; this requirement makes it impractical to fitcurrently available NMR spectrometers into smaller, portable devices.

The DNP method polarizes the spins of electrons in molecules. Thenormally random spins of the many electrons situated around the nucleibeing investigated blur the nuclei's response. DNP forces all electronspins to point in the same direction, enhancing the NMR response fromnon-zero-spin isotopes. This well-known, widely-established method wasfirst developed by Overhauser and Carver in 1953, but at that time, ithad limited applicability for high-frequency, high-field NMRspectroscopy due to the lack of microwave (or gigahertz) signalgenerators. The requisite generators, called gyrotrons, are availabletoday as turn-key instruments, and this has rendered DNP a valuable andindispensable method, especially in determining the structures ofvarious molecules by high-resolution NMR spectroscopy. However,gyrotrons remain cost-prohibitive because they require expensivecomponents, i.e. high-voltage generators, independent permanent magneticfield generators, and deep vacuum devices such as turbomolecular pumps.

Usage of fully non-invasive methods in medical applications requiresnon-invasive methods for the detection of targeted regions (mainlytumors) and their precise positions within the broader area of detection(typically the patient's body).

There are several well-known and widely-used primary approaches thatsupport surgeons in the detection of tumors and their precise positionswithin the body, i.e. biopsy, ultrasound monitoring, positron emissiontomography (PET), X-ray computed tomography (CT), and MRI.

Biopsy is a semi-invasive method that requires some operative treatment,which then has some potential for associated recovery. Biopsy providesexact information regarding the existence of a tumor and its placementwithin the body. However, biopsy does not determine the tumor's size.Thus, upon the biopsy's confirmation of the presence of a tumor, one ormore other methods are generally required for treatment planning. Allother methods support the generation of internal images of the patient'sbody, which are particularly necessary in cases where the tumor affectsan organ.

Ultrasound is a non-invasive method of visualization that uses soundwaves to create images of organs and structures inside the body. It issafe and effective and is commonly used to visualize an in utero fetus,cardiac stress reactions, and other internal bodily processes such asfluids flowing through the body. While ultrasound is effective forvisualizing organs, it does not offer sufficient precision to identifytumors within organs and is not currently used for precision ablation.

Positron Emission Tomography (PET) is a functional imaging techniquethat is used to observe metabolic processes in the body. The systemdetects pairs of gamma rays emitted indirectly by a positron-emittingradionuclide (tracer), which is introduced into the body via abiologically active molecule. Three-dimensional perspectives of tracerconcentration within the body are then constructed by computer analysis.There are several disadvantages of PET technology that should beconsidered. First, PET tracers contain highly radioactive substances,and repeated PET scans may subject the patient to dangerous radioactiveionization. Second, these tracers remain active for only about one hour.This requires clinics to maintain expensive cyclotron systems nearby toproduce these isotopes and tracers. Finally, PET hardware is verydifficult to incorporate into an MRI environment. Large tungsten or leadparts must be situated near the MRI sensors, where they impair theimaging resolution. In order to visualize healthy tissue, the surgeonwill need to employ CT or MRI in conjunction with PET. As a result,although PET-CT is commonly used today, PET-MRI is considered moreexperimental.

X-Ray Computed Tomography (CT) is among the first non-invasive methodsfor visualization of a patient's internal bodily structure. Introducedby Godfrey Hounsfield in 1967, CT employs computer-processedcombinations of many X-ray images taken from different angles to producecross-sectional (tomographic) images (virtual “slices”) of predeterminedareas of a scanned object, allowing the surgeon to see inside the bodywithout cutting. CT produces clear images of bones, can distinguishbetween several different types of tissue, and visualizes tissuedensity. However, it cannot distinguish tumors without the use oftracers; therefore, the combination of PET with CT is required toprovide clear images of the patient's body along with the identifiablelocality of a tumor. CT is less expensive than MRI and is widely usedtoday for overall imaging of internal bodily structure. CT combined withPET is the standard method for tumor detection.

The principal disadvantage of CT is exposure to ionized radiation. Thetotal amount of radiation absorbed by the patient during a CT scan isapproximately equivalent to one year's dose of natural radiation.Accordingly, frequent or repetitious use of CT is not recommended.

MRI is a visualization process that uses a magnetic field and pulses ofradio wave energy to construct real-time images of internal bodies. Inmany cases, MRI provides different information about structures in thebody than can be seen with an CT, ultrasound, or PET scans. Similar toPET, MRI visualization is enhanced by the presence of special substances(markers) intentionally introduced into the body; for example,gadodiamide is used via injection for most MRI applications today. Otheralternatives include 13C-glucose and DNP-activated 13C-glucose, thelatter having been introduced in 2015 by Bastiaansen et al. Usually, MRItracers are based on chemical substances already present in largevolumes in the patient's body, and thus MRI tracers are benign in thequantities needed for MRI. Where CT tracers have a shelf life rangingfrom minutes to hours and need to be prepared in a location that isadjacent to the CT procedure, gadodiamide has a shelf life of years, andother MRI markers either have similar long shelf lives or can beprepared well in advance and need only to be activated by a relativelyinexpensive process adjacent to the MRI procedure.

Today, considerable research and development has improved the qualityand the speed of MRI. Nonetheless, real-time MRI with a deterministic,millisecond response remains very desirable but still unavailable.

Non-Invasive Ablation Methods. The following tumor ablation methods arecurrently used by surgeons: operative resection, chemical, microwave(0.5-2 GHz), ultraviolet, radioactive, and high-intensity focusedultrasound ablation.

Operative Resection today is generally only considered for use if noother method is viable for a given patient. Operative resection isusually very arduous for the patient due to risks associated withopening of the body and to highly complicated and potentially expensiverecovery processes.

Chemical Ablation, i.e. chemotherapy, is normally a non-invasiveablation method. However, this method's principal disadvantages are thegeneral intoxication of the human body with chemicals destructive totissue and its very low selectivity with respect to organ ablation.

Microwave Ablation, sometimes called radio frequency ablation, producesgood results and is gaining popularity. However, this method issemi-invasive in that it requires the insertion of a needle electrode of1-10 mm diameter into the body to support the generation of heat.

Ultraviolet and Radioactive Ablation methods are non-invasive. However,each is accompanied by substantial disadvantages. Specifically,ultraviolet and radioactive methods often destroy (ionize) tissues thatare situated between their ultraviolet or radioactive heat sources andthe target tumor, as well as beyond the target zone of the tumor. Hence,they are useful for breast cancer but not for liver or lung cancer.

High-Intensity Focused Ultrasound (HIFU) ablation is safer thanultraviolet and radioactive ablation. However, HIFU also is notsufficiently accurate or discriminate and will heat inappropriate areasoutside the target zone in a cone pattern. It is also subject to localreflection from bones neighboring the target zone.

MRI Heating: The interaction of a permanent magnetic field and analternate magnetic field (AMF) without DNP and/or without magnetic fieldfocusing is well-known, but has never been used for ablation or heatingor tissues due to its poor spatial accuracy. This poor accuracy stemsfrom the low frequency electromagnetic waves involved in the AMF (100MHz and less); these waves are several meters in length and cannot beaccurately focused on the intersection of the permanent magnetic fieldand the AMF.

Thus, each of these alternative ablation technologies has materialdisadvantages. Hence, prospective inventors of real-time visualizationand surgical ablation methods must overcome the following problems:

-   -   construct a signal acquisition scheme that delivers real-time        imaging;    -   construct an MRI system that allows the focusing of a magnetic        field, AMF, or both at a predetermined region inside a body with        real-time control of this position;    -   reduce equipment costs by constructing a new device as a DNP        polarizer that does not require high voltage generators and        expensive deep vacuum devices such as turbomolecular pumps;    -   construct compact magnets with Halbach structure to improve        magnetic field strength.

SUMMARY

The invention is comprised of the following technological components:

-   -   1. Enhanced multi-nucLEar Generation, Acquisition, and Numerical        Treatment of Nuclear Magnetic Resonance spectra (ELEGANT NMR) is        a processing method for signal transformation that delivers        real-time intermediate data, is stable to carrier frequency        fluctuations, and in the particular case of NMR/MRI applications        is also stable to magnetic field fluctuations.    -   2. Real-time method for processing signals from a repeating        processing method.    -   3. Electron Larmor Microwave Amplifier THReaded On Nuclei        (ELMATHRON) is an apparatus to generate an amplitude-modulated        microwave beam.    -   4. A new method of constructing predetermined magnets from        appropriate magnetic material that allows for focusing the        magnetic field in a target region.

The above-mentioned technological components, alone or in combination,render the following devices and systems possible:

-   -   1. Real-time MRI with or without DNP enhancement.    -   2. Combination of HIFU with proposed real-time MRI guidance.    -   3. Magnetic Resonance Non-Invasive Blade and Magnetic Resonance        Non-Invasive Beam (MR. NIB) are real-time methods with real-time        surgeon guidance and navigation, and which have fully automatic        or semi-automatic options.    -   4. Permanent magnet assembly with focused permanent magnetic        field that also has low field outside the focused region,        securing against magnetic incidents during surgical operation        and treatment.

In addition, applications for the use of MR. NIB include but are notlimited to:

-   -   1. Therapy for the reduction in health/growth of sparse tumors        or other undesired tissue populating one or more regions of the        body.    -   2. Removal of blood clots.    -   3. Activation by controlled heating of blood vessel stents where        the stent is covered by or constructed with materials responsive        to NMR frequencies.    -   4. Acceleration of attraction and blood stream absorption of        undesired chemical compounds (such as aluminum) from cells        having heavy concentrations of said compounds. Once in the        bloodstream, their subsequent elimination from the body is        achievable via natural liver function.    -   5. Acceleration of platinum-based chemotherapy.    -   6. Acceleration of cobalamin effects in the human body.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1: A processing method to convert: FIG. 1A wide-band signals f₁(t),. . . , f_(C)(t) having one or several carrier frequencies; FIG. 1Bwide-band NMR signals s4.

FIG. 2: A processing method to generate: FIG. 2A table H={h_(ks)}_(k,s)^(KS) ^(L) =1′ spectra responses p_(nj)(t), n=1, . . . , N, j=1, . . . ,J, and an estimate of the total number of non-zero-spin isotopes N; FIG.2B intermediate data λ_(k)(t), k=1, . . . , K for further spectrumgeneration from all non-zero-spin isotopes with reference table H; FIG.2C intermediate data r_(nj) ²(t), n=1, . . . , N, j=1, . . . , J forfurther spectrum generation from all non-zero-spin isotopes withreference table H.

FIG. 3: A processing method to convert wide-band NMR signals s4 withcorrelated oscillators s10.

FIG. 4: A processing method to convert a set of continuously measuredexperiments delivering u_(lnj)(t), l=1, . . . , L, n=1, . . . , N, j=1,. . . , J from one set of NMR receivers by collecting severalmeasurements, performing (f10) and (f11) transformations, and solving aminimization (f12) using computational unit s14.

FIG. 5: A processing method to convert a set of continuously measuredexperiments delivering r_(nj) ²(t), n=1, . . . , N, j=1, . . . , J fromone (or one set of) NMR receiver(s) by collecting several measurementsand solving a minimization (f16) using computational unit s16.

FIG. 6: A processing method to convert a set of simultaneously measuredexperiments delivering r_(nj) ²(t), n=1, . . . , N, j=1, . . . , J andsolving a minimization (f16) using computational unit s16.

FIG. 7: A processing method to convert a set of continuously measuredexperiments delivering g_(sj)(t), s=1, . . . , S_(L), j=1, . . . , Jfrom one (or one set) of NMR receiver(s) by collecting severalmeasurements and simultaneously solving minimizations (f15) and (f17)using computational unit s20.

FIG. 8: A processing method to convert a set of simultaneously measuredexperiments delivering g_(sj)(t), s=1, . . . , S_(L), j=1, . . . , J andsimultaneously solving minimizations (f15) and (f17) using computationalunit s20.

FIG. 9: A real-time database method.

FIG. 10: The Electron Larmor Microwave Amplifier THReaded On Nuclei(ELMATHRON). FIG. 10A refers to the main assembly, FIG. 10B shows indetail the top portion, and FIG. 10C shows in detail the printed lineson tube e9 on the bottom of the ELMATHRON.

FIG. 11: A waveform with amplitude modulation produced by ELMATHRON.This is a representative schematic, as the actual total number of wavesinside a pulse is usually larger than shown in the picture and dependson nuclei and pulse type.

FIG. 12: Six coils situated on the edges of a parallelepiped(three-dimensional figure formed by six parallelograms). The totalnumber of turns for each coil may be two or more. The numbers of turnson coils within each subset {1, 2, 3, 4} and {5, 6} are equal, i.e.coils 1-4 must be the same and coils 5-6 must also be the same, butcoils 1-4 can differ from coils 5-6. The optimal number of turns in eachsubset depends on the dimensions of the device, the magnetic field'sstrength, and the electronics used. Depending on the embodiment, eachcoil subset may be comprised of transmitting and/or receiving coils.

FIG. 13: ELEGANT NMR spectrometer embodiment for in-situ measurements,where FIG. 13A refers to the complete assembly, FIG. 13B refers to thecomponent containing the electronics, FIG. 13C refers to the sensorblock for performing measurements in a fluid flow, FIG. 13D refers tothe sensor block when dipped in fluid to be measured, and FIG. 13Edemonstrates how the dipped sensor may be constructed to be suitable forstandard ground glass joints (this embodiment can be constructed with orwithout the ELMATHRON and refers to FIGS. 13-14).

FIG. 14: ELEGANT NMR spectrometer embodiment for in-situ measurementsenhanced by ELMATHRON a4, where FIG. 14A refers to the completeassembly, FIG. 14B demonstrates the connection of receiver coils a25along magnets (a23 and a24), FIG. 14C refers to the sensor block forperforming measurements in a fluid flow, and FIG. 14D refers to thesensor block when dipped in fluid to be measured.

FIG. 15: Embodiments for ELEGANT NMR spectrometer for in-situmeasurements with (FIGS. 15A-15B) and without (FIGS. 15C-15D) theELMATHRON characterizing from the embodiments in FIGS. 13-14 in having amagnet structure with better access of the receiver coil(s) and/or NMRdetector(s) to the measured fluids, albeit lower magnetic fieldstrength. FIG. 15E demonstrates how a dipped sensor may be constructedso as to be suitable for standard ground glass joints (this embodimentcan be constructed with or without the ELMATHRON).

An important difference of these embodiments (FIG. 15) from that inFIGS. 13-14 is that the shape of magnet a1 may curve inward or have anyother shape that improves total magnetic field strength and smoothnessand is also appropriate for embodiments both with and without ELMATHRON.

FIG. 16: ELEGANT NMR spectrometer embodiment with encapsulated permanentmagnets a1 and one ELMATHRON a4 emitting diffracting waves over itsdiffraction grating e7. Fluid sample is supplied continuously throughthe tube or capillary or chromatography column a2. FIG. 16A shows a sideview, and FIG. 16B shows top and bottom views.

FIG. 17: ELEGANT NMR spectrometer embodiment with encapsulated permanentmagnets a1 and two ELMATHRONs a4 emitting diffracting waves a9. Fluidsample is supplied continuously through the capillary or chromatographycolumn a2. FIG. 17A shows a side view, and FIGS. 17B-17C show top andbottom views. Several other embodiments can be considered: magnet a3 maytake different shapes/forms (FIG. 17B with vertical cylinder and FIG.17C with horizontal cylinder) such that its permanent magnetic fieldcovers the large area where the capillary or chromatography column a2 issituated; a6 may be coils and/or optical NMR detectors; and instead ofone or all ELMATHRONs, a transmitter coil situated in parallel with a6may be used.

FIG. 18: ELEGANT NMR spectrometer embodiment with ELMATHRON a4 capableof working in an external magnetic field a26 (from permanent magnets orsuperconductor coil(s)). Fluid sample is supplied continuously throughthe capillary or tube or chromatography column a2. FIG. 18A shows a sideview, and FIG. 18B is a detailed view of the capillary/tube/column a2,receiver coils a6, and receiver electronic PCBs a3.

FIG. 19: Droplet size distribution measurement of a sample with twophases. The same picture demonstrates how magnetization from thestationary phase is transferred to the mobile phase in the case where achromatography column with incorporated NMR sensors is used.

FIG. 20: Magnetic Resonance Non-Invasive Blade as well as MagneticResonance Non-Invasive Beam (MR. NIB) system for real-time MRI and/orreal-time non-invasive surgical applications together with real-timeguidance and optionally unmanned operation.

FIG. 21: A magnet assembly with linear anisotropic (FIG. 21A) andnearly-optimal (FIG. 21B) magnetic polarization and the correspondingcontour-plot of magnetic field strength of an area between magnets.

FIG. 22: A magnet assembly with linear anisotropic magnetic polarizationfor NMR spectrometers without ELMATHRON.

FIG. 23: A magnet assembly with linear anisotropic magnetic polarizationfor NMR spectrometers with ELMATHRON.

FIG. 24: A magnet assembly with nearly-optimal magnetic polarization forNMR spectrometers without ELMATHRON.

FIG. 25: A magnet assembly with nearly-optimal magnetic polarization forNMR spectrometers with ELMATHRON.

FIG. 26: A magnet assembly for a side-NMR embodiment with nearly-optimalmagnetic polarization for NMR spectrometers without ELMATHRON.

FIG. 27: A magnet assembly for a side-NMR embodiment with nearly-optimalmagnetic polarization for NMR spectrometers with ELMATHRON.

FIG. 28: A magnetic alloy, comprising:

-   -   (a) crystals of Co—Fe and/or Sm—Co magnetic alloys;    -   (b) crystals of Mn—Bi and/or Mn—Al and/or any other bismuth        based magnetic alloys;    -   (c) low-melting metals that are able to make low-temperature        liquids with (b), wherein a material phase of the alloy is        metallic.

FIG. 29: A processing and an apparatus for pressing anisotropic magneticpowder into permanent magnets with non-uniform magnetic polarization.This figure additionally demonstrates one example of magnetic structureswith a magnetic area that forces particles of magnetic powder to remainoriented in the prescribed direction.

FIG. 30: A processing method and an apparatus for final magnetization.

FIG. 31: A processing method and an apparatus for casting permanentmagnets with non-uniform magnetic polarization. This apparatus mayincorporate the capability to perform a final magnetization step.

REFERENCE NUMERALS

-   -   s1: Linear filters and/or delay lines. If one or several        elements of this block are implemented with digital signals, a        corresponding numerical approximation may be used.    -   s2: A set of mixers with each mixer receiving a pair of signals        (f_(l) ₁ (t), f_(l) ₂ (t)), l₁, l₂=1, . . . , S_(L) and        delivering its product.    -   s3: Low-pass filter block that is used in parallel with all        passed signals.    -   s4: Receiver coil or optical receiving detector.    -   s5: One or more sequentially-connected amplifiers.    -   s6: A processing block that converts g_(s)(t), s=1, . . . ,        S_(L) to a table H, spectra responses p_(nj)(t), n=1, . . . , N,        j=1, . . . , J, and estimate of the total number of        non-zero-spin isotopes N, solving minimization problem (f15).    -   s7: Mixer and summator block that performs operation (f10).    -   s8: Mixer and summator block that performs operation (f10) in        the case where no long delay lines are used.    -   s9: A marker a substance/mixture containing at least one        non-zero-spin isotope with a priori known spectra and        concentration that is either:    -   situated in the measured substance, or    -   incorporated as the reference unit inside coils s4, or    -   incorporated in the walls of the measuring NMR camera.    -   s10: One or several frequency generators and their signals,        delayed on ¼ period. Each frequency generator has fixed ratio        (a_(n)/b_(n)) to the main frequency generator.    -   s11: A set of mixer pairs with each mixer pair receiving a pair        of signals (f_(l)(t), Re(v_(n)(t))) or (f_(l)(t), Im(v_(n)(t)))        and delivering their products.    -   s12: A processing block that incorporates the method described        in FIG. 3.    -   s13: A block that continuously supplies pipeline data        n_(lnj)(t), l=1, . . . , L, n=1, . . . , N, j=1, . . . , J from        s12 into local storage and delivers it to processing block s14.    -   s14: A processing block that solves minimization problem (f12).    -   s15: A processing block that incorporates the method described        in FIG. 1 followed by the method from FIG. 2.    -   s16: A processing block that solves minimization problem (f16).    -   s17: A block that continuously supplies pipeline data r_(nj)        ^(2(t), n=)1, . . . , N, j=1, . . . , J from s15 into local        storage and delivers said data to processing block s16.    -   s18: A block that gathers data r_(nj) ^(2(t), n=)1, . . . , j=1,        . . . , J from several blocks s15 and delivers said data to        processing block s16.    -   s19: A processing block that incorporates the method described        in FIG. 1.    -   s20: A processing block that simultaneously solves minimizations        (f15) and (f17).    -   s21: A block that continuously supplies pipeline data g_(sj)(t),        s=1, . . . , S_(L) from    -   s19 into local storage and delivers said data to processing        block s20.    -   s22: A block that gathers data g_(sj)(t), s=1, . . . , S_(L),        j=1, . . . , J from several blocks s19 and delivers said data to        processing block s20.    -   s23: Real-time intermediate data generator and sensor.    -   s24: Non-real-time action generator.    -   s25: Non-real-time database updater.    -   s26: Real-time database searcher.    -   s27: Real-time action.    -   e1: A spring that ties tube e9 and plug e4 so that they remain        at the same positions relative to the vessel of ELMATHRON e2.    -   e2: Hermetically-sealed glass and/or ceramic case/vessel of the        ELMATHRON, preferably without any via/hole for power/energy        supply and vacuum supply.    -   e3: The getter.    -   e4: A plug with a non-conductive wave reflector e8 at the        bottom.    -   e5: Shielding situated/printed on the outer side of tube e9,        which reduces undesirable electromagnetic emission.    -   e6: The anode constructed as a thick, monolithic layer on the        inner side of tube e9.    -   e7: Diffraction grating.    -   e8: The wave reflector, constructed as a cone, a flat, or a        focusing/collecting mirror, or other shape of mirror such that        some part of the emitted waves may be reflected back to cathode        e13 to accelerate the cathode's electron emission.    -   e9: Glass and/or ceramic tube situated inside the        hermetically-sealed ELMATHRON's vessel e2; its outer diameter        should be as close as possible to, but a little bit smaller        than, the inner diameter of the vessel e2, preferably with        printed traces on the inner and outer surfaces. The tube walls        should be as small as possible, but only large enough to be        resistant to the peak voltage that occurs at the secondary        winding e16 during operation.    -   e10: An external system or device that provides the permanent        magnetic field.    -   e11: Several parallel traces situated along the main axis of the        ELMATHRON's vessel e2 and printed/placed on the tube e9. All of        the traces on one side are smoothly connected to each other and        to the secondary winding e16, while those on the opposite side        are connected to the diffraction grating e7.    -   e12: Depending on the embodiments, this may be:    -   a feedback control to sustain the cathode e13 at a predetermined        temperature, and/or    -   an electromagnetic beam to heat the cathode e13, and/or    -   an electromagnetic beam to accelerate electron emission from the        cathode e13.    -   e13: The cathode, constructed of tungsten or any other        high-melting metal or alloy; electrically, the cathode behaves        as a shorted turn if heating of the cathode is performed by        inductive and/or electromagnetic methods. It may be covered by a        substance to accelerate electron emission.    -   e14: A primary winding of a cathode heater.    -   e15: The getter block, which serves as an ion pump.    -   e16: The secondary winding of the forward converter, with coils        on the inner and outer sides of the tube e9. The sides may have        windings with different numbers of turns, or one side (inner or        outer) may have no windings with a straight conductive line or        any other connection that does not act as a shorted turn.    -   e17: Several parallel primary windings of the forward converter.        Preferably, each winding is printed on one PCB together with its        powering electronics, and these PCBs are stacked atop each        other.    -   e18: Power supply and control unit for e17.    -   e19: Power supply and control unit for e14, with feedback        control (optical or infrared) to prevent overheating of the        cathode e13.    -   a1: Permanent magnet(s). The magnets may have cylinder shapes        with horizontal    -   axes as shown in FIG. 17C, or any other shapes that permit        better placement of the capillary/tube/column    -   a2: while also supporting a magnetic field of sufficient        strength covering where measurements occur and where the        ELMATHRON vessels are situated.    -   a2: Capillary or tube or chromatographic column with        investigated substance.    -   a3: PCB with receiver electronics.    -   a4: The ELMATHRON vessel.    -   a5: Power supply and control unit of the ELMATHRON.    -   a6: Receiver coils and/or optical NMR detectors situated        on/in/over the capillary/-tube/column    -   a2.    -   a7: Permanent magnet boundaries; permanent magnets a1 are        situated one over and one under the capillary/tube/column a2,        PCB a3, and receiving coils a6.    -   a8: Permanent magnets of the ELMATHRON; these magnets may be        incorporated in the main magnet assembly a1.    -   a9: Interference waves from ELMATHRONs.    -   a10: Thermostat connectors: cooling/heating fluid is dispersed        over these connectors to control the temperature of the        electronics inside the device.    -   a11: Area inside the ELEGANT NMR spectrometer with constant        temperature controlled by fluid thermostatting.    -   a12: Screw threads to screw the block with magnets a16 to the        block with electronics    -   a15.    -   a13: Plugs that connect the coils (a20 or a25) to the        electronics a14.    -   a14: PCB assembly with transmitter and receiver electronics. In        the case of a thermostat connection being used, the PCBs should        be coated with appropriate materials to prevent damage by fluid        thermostatting.    -   a15: Main case of the device, housing the electronics a14.    -   a16: The case for the block with magnets.    -   a17: Gasket for hermetic connection.    -   a18: Data and power supply connector.    -   a19: Wires to connect plug(s) a13 with coil(s) a20 or a25.    -   a20: Receiver and transmitter coil assembly, one embodiment of        the coils assembly described in FIG. 12.    -   a21: Hermetically-sealed non-conductive case that is connected        and incorporated into the magnetic block a16 and that allows        electromagnetic waves to penetrate and generate inductive and/or        electromagnetic coupling from a14 to a4.    -   a22: Flow connectors. One can connect tubes to perform        measurements in flow. In the case of the solid-state and NMR        tube detector embodiment being used, said connectors should        allow an external tube to be placed inside the measurement area        and associated coils. In the case of the embodiment with        ELMATHRON being used, said connectors may be asymmetrical in        order to fulfill conditions on the placement of the external        tube.    -   a23: Permanent magnet in the form of a cylinder with an inner        diameter slightly larger than the outer diameter of the        ELMATHRON vessel a4. Between the ELMATHRON vessel and this        magnet, a special gasket may be installed to keep this        connection hermetic and to ensure that the glass/ceramic case of        the ELMATHRON is not broken through mechanical vibrations and/or        temperature expansion from the magnet cylinder.    -   a24: A permanent magnet in the form of a cylinder with an inner        diameter slightly larger than the outer diameter of the magnet        a23. Wires a19 are situated between said magnet cylinders a23        and a24. The magnets a23 and a24 may be hermetically coupled, in        which case a special gasket should be installed between a23 and        a24.    -   a25: Receiver coils and/or optical NMR detectors.    -   a26: External magnetic field generated by permanent magnets or        superconductor magnets.    -   a27: Ground glass joint.    -   d1: A transmitting wave is absorbed by droplet or stationary        phase material.    -   d2: Droplet or stationary phase material emitting the same        frequency wave or carrier frequency wave spectrum as absorbed in        d1.    -   d3: A transmitting wave is absorbed by solution or mobile phase        material.    -   d4: Solution or mobile phase material emitting the same        frequency wave or carrier frequency wave spectrum as absorbed in        d3.    -   d5: A transmitting wave is adsorbed by material situated on the        surface of a droplet or a stationary phase.    -   d6: Solution material previously excited by magnetization        transfer as in d7 emits a different frequency wave than was        adsorbed in d5.    -   d7: Excited material on the surface of a droplet or a stationary        phase transfers its magnetization to solution or mobile phase        materials situated near the surface of the droplet.    -   n1: A plurality of permanent magnets with the potential for        changing the direction and intensity of the magnetic field by        mechanical movements (coarse tune) and by electromagnetic coils        (fine tune).    -   n2: Receiver coils.    -   n3: PCBs with receiver electronics.    -   n4: ELMATHRON vessel(s).    -   n5: Power supply and control units of ELMATHRON(s) (controlled        in parallel with receivers) with additional potential for        changing the orientation and position of ELMATHRON(s) to change        the directions of their beam(s).    -   n6: Non-uniform magnetic field formed by n1.    -   n7: Electromagnetic beam(s) from the ELMATHRON(s).    -   g1, g2: Permanent magnets with linear anisotropic magnetization        for NMR spectrometers without ELMATHRON.    -   g3, g4: Permanent magnets with linear anisotropic magnetization        for NMR spectrometers with ELMATHRON.    -   g5, g6: Permanent magnets with linear anisotropic magnetization        for MR. NIB technology.    -   g7, g8: Permanent magnets with nearly-optimal magnetic        polarization for NMR spectrometers without ELMATHRON. Top and        bottom boundaries may be flat or some other shape to fit better        into the mechanical assembly and/or for better access of the        receiver coil(s) and/or NMR detector(s) to the measured fluids.    -   g9, g10: Permanent magnets with nearly-optimal magnetic        polarization for NMR spectrometers with ELMATHRON. Top and        bottom boundaries may be flat or some other shape to fit better        into the mechanical assembly and/or for better access of the        receiver coil(s) and/or NMR detector(s) to the measured fluids.    -   g11, g12: Permanent magnets with nearly-optimal magnetic        polarization for MR. NIB technology. Top and bottom boundaries        of both g11 and g12 magnets may be flat or some other shape to        fit better into the mechanical assembly.    -   g13: Receiver and transmitter coils assembly, one embodiment of        the coils assembly described in FIG. 12.    -   g14: Receiver coils or optical NMR detectors.    -   g15: The ELMATHRON vessel.    -   g16: Contour plot of a vertical magnetic field strength        projection using permanent magnets with linear anisotropic        magnetization in MR. NIB technology.    -   g17: Contour plot of a vertical magnetic field strength        projection using permanent magnets with nearly-optimal        magnetization in MR. NIB technology.    -   g18: Molding tool.    -   g19: Molding matrix.    -   g20: Magnetic powder with anisotropy.    -   g21: A set of one or several:    -   permanent magnets, and/or    -   ferromagnetic materials, and/or    -   permanent electromagnets, and/or    -   superconductor electromagnets, and/or    -   any other non-magnetic materials, and/or    -   permanent magnet(s) previously manufactured with the same        technology.    -   g22: One or several coils for the generation of a permanent        magnetic field, consisting of a foil of good-conducting metal.        The total amount of winding in these coils should be sufficient        to generate a permanent magnetic field of at least the same        strength as the magnetic field delivered by nearly-optimal        anisotropically manufactured (sintered, casted, pressed, etc.)        magnets.

Construction of said coils may be accomplished with one coil or severalsections of coils, including coils with different and/or oppositedirections.

These coils should be connected over an electronic or mechanical switchto one or several capacitors, and/or super-capacitors, and/or batteries,and/or power supply units connected in parallel, which should be capableof delivering enough current so that the coils are able to generate apermanent magnetic field of at least the same strength as the magneticfield delivered by anisotropic magnets.

g23: Upper side of a device that prevents the magnetic material g25 frommigrating up during final magnetization. It may comprise additionaljoints (not shown in the figure) that are strong enough to withstand theforce between manufactured magnet g25 and coil(s) g22.

g24: The case of a device that prevents the magnetic material g25 andcoils from migrating during final magnetization.

g25: Manufactured magnetic material prepared for final magnetization.

g26: One or several coils for the generation of a permanent magneticfield and/or heat, consisting of a foil of good-conducting metal. Themelting point of said metal or parts of said coils situated close to g25should be above the casting temperature.

Construction of said coils may be accomplished with one coil or severalsections of coils, including coils with different and/or oppositedirections.

These coils should be connected over an electronic or mechanical switchto one or several capacitors, and/or super-capacitors, and/or batteries,and/or power supply units connected in parallel, which should be capableof delivering enough current so that the coils are able to generate apermanent magnetic field of at least the strength produced by magneticmaterial casted anisotropically.

g27, g28: Upper side and case of a device that holds casted magnets andcoils and may contain one or several temperature sensors.

g29: Additional fluid cooling that may be necessary to regulatetemperature during casting and to ensure appropriate magnetic fieldstrength.

g30: Casting magnetic material.

g31: The same coils as g26, which additionally may have the potential togenerate inductive heating for g30 on the stage in order to increase thetemperature and melting of material in g30.

g32: Crystals of Co—Fe and/or Sm—Co magnetic alloys.

g33: Crystals of Mn—Bi and/or Mn—Al and/or any other bismuth basedmagnetic alloys.

g34: Low-melting metals (In, Bi, Sn, Ga, Tl, Cd, Zn, Pb, Te and others)that are able to make low-temperature liquids with g33.

g35: Alternative embodiment (to g8) for permanent magnets withnearly-optimal magnetic polarization for NMR spectrometers withoutELMATHRON.

g36: Alternative embodiment (to g10) for permanent magnets withnearly-optimal magnetic polarization for NMR spectrometers withELMATHRON.

g37: Additional magnet for FIGS. 15A-15B embodiments that improvemagnetic field strength.

DETAILED DESCRIPTION ELEGANT NMR

The Enhanced multi-nucLEar Generation, Acquisition, and NumericalTreatment of Nuclear Magnetic Resonance spectra (ELEGANT NMR) is aprocessing method constructed according to the following scheme.

Consider FIG. 1B: One or several wide-band coils and/or opticaldetectors s4 receive very weak signals that are usually amplified by oneor more sequential amplifiers s5. The signals are abbreviated asf_(l)(t), 1=1, . . . , C, where C is the total count of input signalsand t is the time domain variable of the measurements. These signals areforwarded to a block s1 of several linear filters and/or delay lines.These linear filters and delay lines may be comprised of passivecomponents or operational and/or differential amplifiers and/or otheranalog circuits, or may be completely implemented digitally. Theresulting signals are abbreviated as f_(l)(t), 1=C+1, . . . , L. Eachlinear filter or delay line has one input and one output, acts on onlyone input signal, and delivers one output signal. All input signals mayparticipate in the generation of signals after block s1 and, forpractical reasons, L should be as small as possible without compromisingthe quality of the results upon a priori conditions, which will bediscussed later. The case where C=L (no linear filters and no delaylines) is also possible.

All f_(l)(t),1=1, . . . , L signals are forwarded pairwise to the mixerblock s2. The same pairs of signals may be used, but are not countedhereafter. A subset of all possible pairs may be used. The total numberof different mixers is denoted as S_(L) and it is, by definition,

$S_{L} \leq {\frac{L( {L + 1} )}{2}.}$

The resulting signals from each mixer are forwarded over a low-passfilter s3 and abbreviated as g_(s)(t), where s=1, . . . , S_(L) is theindex of the mixer. An input pair of each s-th mixer refers to

(f_(ξ_(s)⁽¹⁾)(t), f_(ξ_(s)⁽²⁾)(t)),

where ξ_(s) ⁽¹⁾, ξ⁽²⁾=1, . . . , L. The resulting signals g_(s)(t), byconstruction, are sufficient for reconstructing the pure spectra of allnon-zero-spin isotopes (one input/coil setup in FIG. 1) and the spatialdistribution of these spectra (multi-input/multi-coil setup in FIG. 1,for example, for MRI).

Assume a pure spectrum of each n-th non-zero spin isotope (n=1, . . . ,N) of the investigated substance is written as:

$\begin{matrix}{{{p_{n}(t)} = {{\sum\limits_{m = 1}^{M_{n}}{A_{n\; m}e^{{i\; \omega_{n\; m}t} + {ib}_{n\; m}}}} \in {\mathbb{C}}}},A_{n\; m},{b_{n\; m} \in {\mathbb{R}}},{\omega_{n\; m} \in {\mathbb{C}}},{{p_{n}(t)} = {{r_{n}(t)}e^{i\; {\theta_{n}{(t)}}}}},{{r_{n}(t)} = {{p_{n}(t)}}},{r_{n}(t)},{{\theta_{n}(t)} \in {\mathbb{R}}}} & (1)\end{matrix}$

where A_(nm) are amplitudes, b_(nm) are phases, and ω_(nm) are resonanceresponses in the n-th non-zero-spin isotope spectrum. Additionally,assume that in a given magnetic field, the carrier frequency (Larmorfrequency) of the n-th non-zero-spin isotope is W_(n). The signalcollected by the wide-band receiver coil/optical detector is thenwritten as:

$\begin{matrix}{{\sum\limits_{i = 1}^{N}{{Re}( {e^{{iW}_{n}t}{p_{n}(t)}} )}},} & ({f2})\end{matrix}$

where Re(x) and Im(x) are the real and imaginary components of thecomplex number x. Taking into account that W_(n)>>ω_(nm), linear filtersand/or delay lines transform the signal (f2) to:

where

$\begin{matrix}{{{f_{l}(t)} = {{\sum\limits_{n = 1}^{N}{Q_{l\; n}{{Re}( {e^{{iW}_{n}t}e^{i\; \beta_{l\; n}}{p_{n}( {t + \delta_{l}} )}} )}}} = {\sum\limits_{n = 1}^{N}{{r_{n}( {t + \delta_{l}} )}Q_{l\; n}{{Re}( e^{{i\; W_{n}t} + {i\; \beta_{l\; n}} + {i\; {\theta_{n}{({t + \delta_{l}})}}}} )}}}}},} & ({f3})\end{matrix}$

-   -   Q_(ln) ϵ        and β_(ln) ϵ        are filter parameters in the case of linear filters being        applied (δl=0),    -   δ_(l) is a delay in the delay line (Q_(ln)=1 and        β_(ln)=W_(n)δ_(l)).

Blocks with arbitrary δ_(l), Q_(ln), and β_(ln) can be also considered.

It is also evident that if two delay lines with delays δ₁ and δ₂ areused in the mixer block s2, this is equivalent to forwarding theoriginal signal from the block s4 and the signal with delay |δ₁−δ₂| tosaid mixer, and thus this scenario is not further considered.

Hereafter, the short delay line refers to delays much less than oneperiod of any ω_(nm), and the long delay line refers to all otherdelays. In the case of a linear filter or short delay line being used,formula (f3) may be considered as

$\begin{matrix}{{{f_{l}(t)} = {{\sum\limits_{n = 1}^{N}{Q_{\ln}{{Re}( {e^{{iW}_{n}t}e^{i\; \beta_{\ln}}{p_{n}(t)}} )}}} = {\sum\limits_{n = 1}^{N}{{r_{n}(t)}Q_{\ln}{{Re}( e^{{{iW}_{n}t} + {i\; \beta_{\ln}} + {i\; {\theta_{n}{(t)}}}} )}}}}},} & ({f4})\end{matrix}$

because p_(n)(t)≅p_(n)(t+δ_(l)) if δ_(l) is much less than any ω_(nm).

Each pair

(f_(ξ_(s)⁽¹⁾)(t), f_(ξ_(s)⁽²⁾)(t))

of these signals (f3), forwarded over a mixer and then over a low-passfilter, is described as:

$\begin{matrix}{{g_{s}(t)} = {\sum\limits_{n = 1}^{N}{Q_{\xi_{s}^{(1)}n}Q_{\xi_{s}^{(2)}n}{r_{n}( {t + \delta_{\xi_{s}^{(1)}}} )}{r_{n}( {t + \delta_{\xi_{s}^{(2)}}} )}\{ {{{\cos( {\beta_{\xi_{s}^{(1)}n} - \beta_{\xi_{s}^{(2)}n}} )}{\cos( {{\theta_{n}( {t + \delta_{\xi_{s}^{(1)}}} )} - {\theta_{n}( {t + \delta_{\xi_{s}^{(2)}}} )}} )}} - {{\sin( {\beta_{\xi_{s}^{(1)}n} - \beta_{\xi_{s}^{(2)}n}} )}{\sin( {{\theta_{n}( {t + \delta_{\xi_{s}^{(1)}}} )} - {\theta_{n}( {t + \delta_{\xi_{s}^{(2)}}} )}} )}}} \}}}} & ({f5})\end{matrix}$

Now consider

$\begin{matrix}{{{r_{n}( {t + \delta_{\xi_{s}^{(1)}}} )}{r_{n}( {t + \delta_{\xi_{s}^{(2)}}} )}{\cos( {{\theta_{n}( {t + \delta_{\xi_{s}^{(1)}}} )} - {\theta_{n}( {t + \delta_{\xi_{s}^{(2)}}} )}} )}},{and}} & ({f6}) \\{{r_{n}( {t + \delta_{\xi_{s}^{(1)}}} )}{r_{n}( {t + \delta_{\xi_{s}^{(2)}}} )}{{\sin( {{\theta_{n}( {t + \delta_{\xi_{s}^{(1)}}} )} - {\theta_{n}( {t + \delta_{\xi_{s}^{(2)}}} )}} )}.}} & ({f7})\end{matrix}$

Some terms in (f6) and (f7) may be equal to each other, for example inthe case where a small δ is used, and in other above-mentioned cases.These terms may be enumerated by the index k=1, . . . , K and assumed asλ_(k)(t), so that equation (f5) transforms to

$\begin{matrix}{{{g_{s}(t)} = {\sum\limits_{k = 1}^{K}{{\hat{h}}_{sk}{\lambda_{k}(t)}}}},{s = 1},\ldots \mspace{14mu},S_{L}} & ({f8})\end{matrix}$

where ĥ_(sk) is constructed as the corresponding terms

$\begin{matrix}{{Q_{\xi_{s}^{(1)}n}Q_{\xi_{s}^{(2)}n}{\cos( {\beta_{\xi_{s}^{(1)}n} - \beta_{\xi_{s}^{(2)}n}} )}},{Q_{\xi_{s}^{(1)}n}Q_{\xi_{s}^{(2)}n}{\sin( {\beta_{\xi_{s}^{(1)}n} - \beta_{\xi_{s}^{(2)}n}} )}}} & ({f9})\end{matrix}$

according to said enumeration of λ_(k)(t).

Taking into account that only S_(L) pairs of

(f_(ξ_(s)⁽¹⁾)(t), f_(ξ_(s)⁽²⁾)(t))

are available, the matrix Ĥ={ĥ_(sk)}ϵ

S_(L)×K is constructed, with H={h_(ks)}ϵ

K×S_(L) built as a pseudo-inverse matrix of Ĥ, i.e. HĤ=I, where Iϵ

K×K is an identity matrix. The computation of H can be performed on anyappliance unit using well-known algorithms based on a singular valuedecomposition (SVD).

Hence, the set of g_(s)(t), s=1, . . . , S_(L) may be transformed to theset of λ_(k)(t) using just one real-time matrix-by-matrix multiplicationblock s7 (FIG. 2B):

$\begin{matrix}{{{\lambda_{k}(t)} = {\sum\limits_{s = 1}^{S_{L}}{h_{ks}{g_{s}(t)}}}},{{\text{∀}k} = 1},\ldots \mspace{14mu},K,} & ({f10})\end{matrix}$

and this block may be implemented with digital and/or analog signals.

In the case where λ_(k)(t) refers to the appropriate term of (f6) onwhich the s-th pair of (f5) has no long delay lines, λ_(k)(t) refers tor_(n) ²(t) with corresponding index n and the term (f7) is always equalto zero, so the set of g_(s)(t), s=1, . . . , S_(L) is transformed tothe set of r_(nj) ²(t) by one real-time matrix-by-matrix multiplicationblock s8 as is demonstrated in FIG. 2C.

Hence, by this construction, r_(n)(t)

-   -   is weakly dependent on fluctuations in the permanent magnetic        field,    -   is generated with several microsecond delays after the initial        signal appears,    -   already contains enough information for MRI and can be        transformed to pure NMR spectra, and    -   r_(n)(t) does not require long delay lines and precise        oscillators for its generation.

Now consider that all r_(n)(t), n=1, . . . , N are generated from asubset of λ_(k)(t). Then, the remaining subset of λ_(k)(t), according todefinitions in (f6) and (f7), has only the unknown terms

$\begin{matrix}{{{\cos( {{\theta_{n}( {t + \delta_{\xi_{s}^{(1)}}} )} - {\theta_{n}( {t + \delta_{\xi_{s}^{(2)}}} )}} )}\mspace{14mu} {and}}\text{}{{\sin( {{\theta_{n}( {t + \delta_{\xi_{s}^{(1)}}} )} - {\theta_{n}( {t + \delta_{\xi_{s}^{(2)}}} )}} )},}} & ({f11})\end{matrix}$

of which θ_(n)(t) may be computed by several arithmetic operationsinvolving arc sin and arc cos, or approximated by well-knownleast-squares or total least-squares minimization methods.

The generation of θ_(n)(t) (but not r_(n)(t)) is dependent on themagnetic field fluctuation and requires long delay lines that usuallynecessitate crystal oscillators.

When at least two different non-zero-spin isotopes and at least tworeceiving coils are available in the investigation area and both isotoperesponses affect the input signal, the magnetic field fluctuation iscomputed so that all pure isotope spectra are resistant to magneticfield fluctuations.

To do this, consider that {tilde over (θ)}_(inj)(t) is computed for allnon-zero-spin isotopes (n=1, . . . , N), all receiving coils (j=1, . . ., J), and for several repetitions (i=1, . . . , I). The repetitions arecollected for the same mixture from all receiving coils, but overdifferent time durations.

Consider that the NMR receiving coils are made of differentnon-zero-spin isotopes; the NMR spectra of these coils are measured.This measurement may be done once upon calibration of the device,without any substance/mixture for measurement.

Consider that these spectra are computed and stored at

{circumflex over (P)} _(nj)(t)=r _(nj)(t)e ^(i{circumflex over (θ)})^(nj) (t)

Since the fluctuation of the magnetic field during measurement israndom, but the fluctuation of the magnetic field of each isotopespectrum is the same, if collected simultaneously the followingminimization may be considered:

$\begin{matrix}{{\begin{matrix}\min \\{{\psi_{n}(t)},{ɛ_{i}(t)}}\end{matrix}{\int{\sum\limits_{i,n,j}{{{{{\overset{\sim}{\psi}}_{inj}(t)} - {( {{\hat{\psi}}_{nj} + {\psi_{n}(t)}} ){ɛ_{i}(t)}}}}_{2}^{2}{dt}}}}},{{\psi_{n}(t)} = e^{i\; {\theta_{n}{(t)}}}},{{{\overset{\sim}{\psi}}_{inj}(t)} = e^{i\; {{\overset{\sim}{\theta}}_{inj}{(t)}}}},{{{\hat{\psi}}_{nj}(t)} = e^{i\; {{\hat{\theta}}_{nj}{(t)}}}},{{ɛ_{i}(t)} = e^{i\; {\epsilon_{i}{(t)}}}},} & ({f12})\end{matrix}$

where θ_(n)(t) is the pure phase without fluctuation and ϵ_(i)(t) is thefluctuation of the magnetic field in the i-th measurement. An algorithmto compute θ_(n)(t) according to the minimization of (f12) is describedin Appendix 1.

Hence, this approach provides a robust method for obtaining pure spectraincluding phase with good accuracy for any substance or mixture, even ifthe measured material contains only one non-zero-spin isotope.

A power series of large delay lines, based on δ, 2δ, 4δ . . . with dozenof entries, and

$\begin{matrix}{\delta \simeq {\frac{1}{100}{\min\limits_{nm}\omega_{nm}^{- 1}}}} & ({f13})\end{matrix}$

is suggested as a good working example, but any other series of largedelay lines with a similar range and distribution of δ may also provideappropriate results.

Alternatively, one or several periods of input signals of length (f13)may be stored and used several additional times to generate storedsignal in digital and/or analog form for different δ upon the arrival ofan input signal.

Consider that δ⁻¹ is roughly equal to the cutoff frequency of thelow-pass filter s3, and during δ time the signal can be stored. Thenseveral (not more than 20) storing blocks numbered sb=1, . . . areallocated, and each period of time of length δ is counted with thecounter cnt=0, . . . . Then, if the condition cnt&((1<<sb)−1)==0,written according to C-language notation, is true, the current signal isstored into the sb-th block. Each time, all stored blocks are used asf_(l)(t) signals in the input of s2 (FIG. 1). This drastically savescomponent counts and allows the implementation of a robust and stablescheme for the computation of θ_(n)(t).

Many other techniques for generating δ may be used to provide a goodbalance between hardware resources and the total number of different δvalues, which are determined by each particular implementation case.

To improve numerical stability during the computation of θ_(n)(t), thetotal least squares method or the following least squares method aresuggested:

                                          (f14) $\begin{matrix}\min \\{\theta_{n_{k}}(t)}\end{matrix}{\int{\sum\limits_{k}{{{{\lambda_{k}(t)} - {{r_{n_{k}}( {t + \zeta_{k}^{(1)}} )}{r_{n_{k}}( {t + \zeta_{k}^{(2)}} )}\{ {{\eta_{k}^{(1)}{\cos ( {{\theta_{n_{k}}( {t + \zeta_{k}^{(1)}} )} - \mspace{220mu} {\theta_{n_{k}}( {t + \zeta_{k}^{(2)}} )}} )}} + {\eta_{k}^{(2)}{\sin ( {{\theta_{n_{k}}( {t + \zeta_{k}^{(1)}} )} - {\theta_{n_{k}}( {t + \zeta_{k}^{(2)}} )}} )}}} \}}}}_{v}^{v}{dt}}}}$

in any ν-norm ∥.∥_(ν), with 1≤ν≤∞, where

-   -   η_(k) ⁽¹⁾=1 and η_(k) ⁽²⁾=0 if the cos term of (f6) is used,    -   η_(k) ⁽¹⁾=0 and η_(k) ⁽²⁾=1 if the sin term of (f7) is used,    -   λ_(k) ⁽¹⁾ and λ_(k) ⁽²⁾ are corresponding delays in long delay        lines in (f6) and (f7), and    -   n_(k) is the corresponding index of the n-th isotope in the        λ_(k)(t) term in (f6) and (f7).

There are many possible methods for choosing linear filters or delaylines, and for how the sequences of said linear filters and delay linesare forwarded to the mixers. The best implementation depends on hardwareavailability and properties. Larger numbers of linear filters or mixersmay provide better signal stability. During the construction of blockss1 and s2, the parameters of these blocks should provide entries formatrices H and Ĥ in such a way that the full numerical rank of H (and Ĥ)must be greater than or equal to the total amount of differentnon-zero-spin isotopes situated in the investigated/measurement area.The matrix Ĥ (and H) should be as close as possible to the identitymatrix to save hardware resources during the implementation of blocks s1and s2, and to provide numerical stability and accuracy.

Every signal in f, g, r, λ and h in the described method may be analogor digital. At any point in the process between blocks s1, s2, s3, s4,s5, s6, s7, s8, one or several analog to digital converters (ADCs)and/or one or several digital to analog converters (DACs) can beincorporated to convert between signal types. Any of the blocks s1, s2,s3, s5, s7 and s8 can be implemented through analog and/or digitalmeans. In each particular case, the use of digital, analog, or a mix ofdigital and analog signals is dependent upon component counts, costs,accuracy, average signal frequency, and many other factors.

Additional attention should be given to the use of digital signals inblocks s1 and s3. Linear filters of digital signals may be implementedwith finite difference, weighted sum methods, or linear subspace methodsapplied to the signals that are discretized in a time domain, includingnumerical approximation and numerical rounding-off. In this patentapplication, this type of approximation, i.e. finite difference,weighted sum methods, linear subspace methods, and other similar methodsare considered in parallel to the linear filters and delay lines anddeliver the results in a manner that is approximately equal to resultsachieved by linear filters and delay lines.

One additional feature of the ELEGANT NMR method stems from thegeneration of the table H={h_(ks)} during measurements, as is proposedin FIG. 2A at block s6 according to the solution of the minimizationproblem:

                                          (f15) ${\begin{matrix}\min \\{N,Q_{\xi_{s}^{(1)}n_{k}},Q_{\xi_{s}^{(2)}n_{k}},\beta_{\xi_{s}^{(1)}n_{k}},\beta_{\xi_{s}^{(2)}n_{k}},{r_{n_{k}}(t)},{\theta_{n_{k}}(t)}}\end{matrix}{\int{\sum\limits_{s = 1}^{S_{L}}{{{g_{s}(t)} - \; {\sum\limits_{k = 1}^{K}{{\hat{h}}_{sk}{\lambda_{k}(t)}}}}}_{v}^{v}}}} + {\sum\limits_{k = 1}^{K}{{{{\lambda_{k}(t)} - {{r_{n_{k}}( {t + \zeta_{k}^{(1)}} )}{r_{n_{k}}( {t + \zeta_{k}^{(2)}} )}\{ {{\eta_{k}^{(1)}{\cos ( {{\theta_{n_{k}}( {t + \zeta_{k}^{(1)}} )} - \mspace{220mu} {\theta_{n_{k}}( {t + \zeta_{k}^{(2)}} )}} )}} + {\eta_{k}^{(2)}{\sin ( {{\theta_{n_{k}}( {t + \zeta_{k}^{(1)}} )} - {\theta_{n_{k}}( {t + \zeta_{k}^{(2)}} )}} )}}} \}}}}_{v}^{v}{dt}}}$

in any ν-norm ∥.∥_(ν), with 1≤ν≤ω taking into account (f9). Thisparticular type of minimization is unknown in general, but many similaralgorithms based on the multidimensional decomposition proposed byHarshman in 1970 are known. A scientific theory for the unique solutionof this decomposition was introduced by Kruskal in 1977, and manysimilar applications including NMR have already been discussed in thework of Sidiropolis (2001), Ibragimov (2002), Tugarinov (2005), andHiller (2009). Thus, together with analytical gradient generationmethods proposed by the authors in 2017, the problem (f10) may besolved. The theory of a solution based on alternating least-squares(ALS) iterations is clearly described in the chapter “sparse three-waydecomposition” of Ibragimov (2002), and a highly efficientimplementation algorithm is attached in the source listing (Appendix 2)of this patent application. Even though this method has only a monotonicconvergence, with the use of some accelerations discussed in thereferences above, this method provides a good and stable convergence.

The method (f15) may be used in the following cases:

-   -   if only a few mixers are available in s2, and/or    -   if a set of isotopes in the measurement area is changed, and/or    -   to improve the accuracy of generated data.

The ELEGANT NMR may be additionally used for any single- and multi-bandsignals in applications other than NMR and MRI.

NMR Signal Processing with Many Input Coils

A method comprising long delay lines and/or resonators provides a veryrobust and simple solution for obtaining pure spectra from allnon-zero-spin isotopes, but long delay lines and resonators oftenrequire more complicated and expensive hardware. In addition, thespectra appear only with certain time delays, caused by processing thelong delay line. Hereafter, systems without long delay lines arepreferably considered, while taking into account that long delay linesand/or the method described in FIGS. 3-4 will improve results if theirusage is possible with available hardware.

The embodiments discussed above are applicable for one or several inputsignals; however, up to now, mainly the cases with exactly one inputsignal have been discussed. Two primary situations where several inputsignals are available are as follows:

-   -   one or more receivers perform measurements of a continuous        process, and during this process, the relative response spectrum        may change, so that the j-th entry refers to the j-th        measurement in time (FIGS. 5 and 7); and    -   each j-th receiving coil generates its own data r_(nj)(t) or        g_(sj)(t) with different response spectra (FIGS. 6 and 8).

Different response spectra may occur in the following cases:

-   -   a continuous chemical process (chemical synthesis) is measured,        and the relative concentrations of substances may change over        time;    -   measurements occur in a detector for liquid chromatography,        HPLC, or uHPLC;    -   measurements occur through multi-dimensional NMR experiments,        such as NOESY and multidimensional NMR spectrometry;    -   an array of detectors is used for MRI, where each detector is        situated in its particular place and receives a linear        combination of responses from the excited area.

Hence, all embodiments mentioned above deliver several sets of r_(nj)(t)or g_(sj)(t), and each of these sets has similar spectra with variationsin amplitudes A_(nm) and phases b_(nm), and these sets are obtained froms15 or s19 sequentially or simultaneously in time.

Assume an index j=1, . . . , J refers to the number of sets in theseexperiments (FIGS. 5-8).

Joint usage of several stored signals r_(nj)(t) by the computationalblock s16 generates pure resonance frequencies ω_(nm), amplitudesA_(nm), and phases b_(nm), as well as A_(jnm), b_(jnm) variations alongthe j-th direction. This solution may be obtained by:

$\begin{matrix}{{\min\limits_{A,b,\omega}{\sum\limits_{n}{\sum\limits_{j}{\int_{- \infty}^{+ \infty}{{{{r_{jn}(t)} - {{\sum\limits_{m = 1}^{M_{n}}{A_{nmj}e^{{ib}_{nmj}}e^{i\; \omega_{nm}t}}}}}}_{v}^{v}{dt}}}}}},} & ({f16})\end{matrix}$

in any ν-norm ∥.∥_(ν), with 1≤ν≤∞ as is demonstrated in FIGS. 5 and 6.

Joint usage of several stored signals g_(nj)(t) by the computationalblock s20 generates pure resonance frequencies ω_(nm), amplitudesA_(nm), and phases b_(nm), as well as A_(jnm), b_(jnm) variations alongthe j-th direction. This solution may be obtained by:

$\begin{matrix}{{\min\limits_{A,b,\omega}{\sum\limits_{n}{\sum\limits_{j}{\int_{- \infty}^{+ \infty}{{{{{r_{jn}(t)}e^{i\; {\theta_{jn}{(t)}}}} - {\sum\limits_{m = 1}^{M_{n}}{A_{nmj}e^{{ib}_{nmj}}e^{i\; \omega_{nm}t}}}}}_{v}^{v}{dt}}}}}},} & ({f17})\end{matrix}$

in any ν-norm ∥.∥_(ν), with 1≤ν≤∞ by joint minimization with (f15), asis demonstrated in FIGS. 7 and 8.

These minimization problems are solved by standard and robustleast-squares minimization methods that nowadays available in manytextbooks (for example, “Numerical Optimization” by Nocedal, Springer,USA, 2006, 664p), preferably with the accelerations discussed in theauthors' work of 2017. Its general theory and data flow chart werediscussed in the 2002 paper by Ibragimov, and the implementation of thisminimization procedure on a generic computer with a GNU C99 compiler isdescribed in Appendix 2.

The methods described above generate g_(s)(t) and λ_(n)(t) in real timewith delays of only a few microseconds between s4 and s7 or s8. However,the generation of pure resonance frequencies ω_(nm), amplitudes A_(nm),and phases b_(nm) requires some unpredictable delays, because either

-   -   the numerical iterative approach is used in s16 or s20, where        (f16) or (f17) is solved, or,    -   one must wait until the necessary data are collected for s17 or        s21.

Real-Time MRI

To overcome the problem of unpredictable delays in a spatiallynon-homogeneous case (for example, MRI), the following processing methodis suggested. Suppose all receivers are situated at their particularplaces. Then, each coil s4 receives a linear combination of manyelectromagnetic responses from excited mixtures with shifted phases andattenuation related to the distance that the electromagnetic wavestravel before being absorbed by the receiver coil. In this circumstance,signals in s1 remain linear combinations with the same coefficients,g_(s)(t) are linear combinations of the original signals, and anenhanced matrix H={h_(kjs)} can be constructed so that

$\begin{matrix}{{\lambda_{kj}(t)} = {\sum\limits_{s = 1}^{S_{L}}\; {h_{kjs}{{{gs}(t)}.}}}} & ({f18})\end{matrix}$

Thus, the real-time generation of λ_(kj)(t) in s7 delivers pure NMRspectra from each electromagnetic source, i.e. the 3D magnetic resonanceimage of the investigated object.

The key advantage of this approach is in the low count of linearfilters, delay lines, and mixers to be used, in comparison to the totalamount of said components needed to implement all independent schemes(f10) for each receiving coil and then perform a standard MRIreconstruction algorithm.

To get the best possible configuration of linear filters, delay lines,and mixers and then determine appropriate coefficients of the matrix H,the following algorithm may be used.

ALGORITHM Nr. 1:

-   -   1. A finite element grid for discretization of the measurement        area FEM₁, . . . , FEM_(NFEM) is constructed.    -   2. The three-dimensional positions of receiving coils are stored        in Coil₁, . . . , Coil_(NCoil)ϵ        ³.    -   3. A target set of non-zero-spin isotopes for investigations is        chosen, for example, I_(n)=1, . . . , NI: 1H, 13C, 14N, 15N and        31P.    -   4. A magnetic strength and the corresponding Larmor frequencies        for each target isotope and for each finite element are computed        according to the permanent magnet composition.    -   5. A coefficient of decay of electromagnetic radiation from each        finite element position FEM_(i) to each receiver coil position        Coil_(j) is computed and stored in DC_(ij).    -   6. An initial combination of linear filters, delay lines, and        mixer connections for all available coils is guessed and stored        in a structure S.    -   7. For each FEM_(i), i=1, . . . , NFEM and each particular        isotope I_(n):        -   Assume that only the FEM_(i) source of electromagnetic            radiation is available and has unit value; then the            corresponding g_(s)(t) is computed according to formulas            (f1)-(f5) and DC_(ij). The computed function g_(s)(t) should            be transformed to the spectral domain by Fourier            transformation into a vector g_(sx), x=1, . . . , X, where x            is the discretized index of the spectral domain. The            resulting data are stored in h_(I) _(n,i,s,x) along the x            index.    -   8. Pairs of indexes I_(n) and i, as well as s and x in the        four-dimensional array h_(I) _(n,i,s,x) , should be joined so        that the two-dimensional array H H of size (NI*NFEM)×(S_(L)*NX)        is constructed.    -   9. The condition number of the matrix H H should be computed.    -   10. Said condition number should be minimized by any standard        minimization algorithm according to the variation of the S set.    -   11. When said optimization converges, the pseudo-inverse of this        matrix should be computed, then remapped back to the        four-dimensional array. Its x index refers to the appropriate        Larmor frequency of the corresponding finite element; the        corresponding value should be stored in the three-dimensional        array H and used in (f18).

Even through the described algorithm is computationally complex and mayrequire a supercomputer to complete the job, it should need to beperformed only one time before the equipment starts operation; theresulting data may be stored for further usage.

Hence, from just one real-time measurement (several milliseconds), thecomplete MRI image can be reconstructed in only a few milliseconds. Thisfact opens new possibilities for real-time MRI visualization andguiding.

Real-Time Method for Obtaining Signals from Repeating Processing Method

To illustrate this method, consider one practical example where it maybe used. Suppose a surgical operation is intended. However, instead of areal human surgeon, a surgical robot will perform this operation.

The patient and the patient's organs may react to the pain in about 0.1s, so the surgical scalpel should be accurate and situated with feedbackcontrol requiring much less than this 0.1 s period. Sensors that measurethe scalpel and patient body configurations should report their datamuch faster, with the delay being no more than several milliseconds.

The mechanical system of the surgical robot is fast, and can move itstools (i.e. the scalpel) quickly enough that any arbitrary configurationis achievable in several milliseconds.

However, the numerical computation of mechanical movements according tothe responses of these sensors and information about the operation areso complex that a state-of-the-art appliance unit requires severalseconds to complete the computation, ruining any possibility ofperforming this operation in real time.

Said appliance unit is affordable and compact in size, so thousands ofappliance units may be installed in a hospital. However, theircomputations cannot be parallelized in such a way that the computationswill always complete in several milliseconds. Therefore, it is dangerousto apply this straightforward solution in a real environment.

The proposed method provides a real-time and deterministic response, sothat the surgical robot can determine its next action in real time orcan promptly stop a harmful action if the surgical robot does not haveenough information on what it should do next.

Hence, this example will demonstrate how to construct a processingmethod that may react in real time based on information obtained fromone or several sensors.

A brief scheme of this real-time method is described in FIG. 9. Allinvolved processes operate in time slots, hence each is marked with itsso-called ϕ-th time step.

The method (ALGORITHM Nr. 2) is comprised of the following four parts:

Component 1. A real-time intermediate data generator and sensor s23.This may be any chemical or other sensor that measures some physicaland/or chemical properties. The sensor should deliver measurement datain real time, i.e. with deterministic delay such that the length of thisdelay is below the acting time of the total system. At each time step,this block delivers said intermediate data set z_(ϕ). This data set isusually digital and is represented as an array of digits.

Component 2. Non-real-time action generator s24. This block receivesdata z_(ϕ) upon its availability and performs a computation. The resultof this computation is a special data set y_(ϕ) that can be used inblock s27 to perform a real-time action, or a parametric data set thatmay be used in block s27 to generate and perform a real-time action.Computational time for this step is unpredictable. The computation maybe interrupted if it takes too much time. To be able to completecomputations for most of the input data that arrives at each time step,one or several computational units can work in parallel. When new data(z_(ϕ+1)) arrives, it is assigned to the first free appliance unit. Ifno free units are available, either the next-arriving data is skipped orthe oldest ongoing computation over all appliance units is discarded andthis free unit is allocated to the new data set z_(ϕ+1).

In the example above, the surgical robot generates how it should behave,i.e. how to set its motors and actuators for the current patientconfiguration, for example, breathing. These computed results may bereused later when the patient re-enters the same predictableconfiguration.

Component 3. Non-real-time database updater s25. This block receives apair of data sets, z_(ϕ) and y_(ϕ), when both are ready and incorporatesthem into a database D. The database containing already-incorporateddata sets from time steps 1, . . . , ϕ is abbreviated as D_(ϕ).

This database may be organized by many different methods. Mostimportantly, the database should possess the property of searching itsentries in real time, within a deterministic amount of time.

Similar to the step for the non-real-time action generator, thecomputational time for this step may be unpredictable. The computationmay be interrupted and this data set discarded if the computation takestoo much time. To be able to complete computations for most of the inputdata that arrives at each time step, one or several computational unitsworking in parallel may be constructed and perform the same way as incomponent 2.

In the example above, the surgical robot collects data from sensors forall possible configurations of patient's body during the patient'sbreathing and moving periods and stores these configurations in thedatabase, i.e. “learning” patient behavior and “learning” how to performthe surgical operation.

Component 4. Real-time database searcher s26. This block receives theactual intermediate data z_(ϕ) from the real-time intermediate datagenerator and sensor, and searches and matches this data against theactually available database. Normally, the database that is availablefor this moment contains only entries that are far behind in time, i.e.the database D_(ϕ−k), with k>>1. In the case where matching of z_(ϕ)occurs, the corresponding vector {tilde over (y)} is delivered. When nomatch is found, then no answer is delivered. By construction, if thedatabase is trained on appropriate data in the previous steps, thismatching delivers a real-time response and bypasses the intensivecalculations which have unpredictable computational times.

Hence, most deep learning algorithms, and/or support vector machinealgorithms, and/or low rank approximation and linear subspace methodsmay be used for the construction of this database, with the restrictionthat searching and matching in the database is always a deterministicprocess.

Matching of test data against an established database may be performedby

-   -   exact match,    -   approximate match in least-squares or any other suitable norm,    -   match to a linear combination of two or several datasets, so        that the resulting vector y is the linear combination of        appropriate y vectors to z vectors.

In the example above, in the case of the surgical robot beingsufficiently trained, it performs real-time actions without any helpfrom a human surgeon and can be much more precise and accurate.

Thus, execution of real-time actions according to arbitrary real-timeresponses from sensors is demonstrated, with a wide range of potentialchemical compositions and spatial configurations detectable by thosesensors in time-critical applications. Many other useful applications ofthese results may be easily outlined, and are discussed in the followingsubsections.

Real-Time Chemical Switch

Consider that measurements are performed on a production line, where oneor several concentrations of substances play an important role, and somedevices/valves should be switched if the concentration of one or severalsubstances goes outside of predetermined boundaries. Usage of thesuggested method solves this problem: if measurement and databaseconstruction are performed, one can monitor desired substances and/ormixtures in real time. If matching by s26 occurs, the switch takesplace.

NMR Signal Processing with Correlated Resonators

In the case of a resonator or internal clock being used with the NMRprocessing method, the following approach is suggested.

Consider FIG. 3: One or several wide-band coils and/or optical detectorss4 receive very weak signals that are usually amplified by one or moresequential amplifiers s5. The signals are abbreviated as f_(l)(t), l=1,. . . , L, where L is the total count of input signals and t is the timedomain variable of the measurements. Based on a priori information aboutthe magnets and non-zero-spin isotopes in use, one or several frequencygenerators s10 and their signals, delayed by ¼ period, are used. Signalsfrom said frequency generators are abbreviated as v_(n)(t), n=1, . . . ,N, so that v_(n)(t) is a complex function whose real part refers to thesignal and whose imaginary part refers to the delayed signal from thesame generator.

All f_(l)(t), l=1, . . . , L signals are forwarded pairwise withv_(n)=1, . . . , N to the mixer block s11, so that each pair iscomprised of one f and one s signal. The resulting signals from eachmixer are forwarded over a low-pass filter s3 and abbreviated asu_(ln)(t), where l is the index of the input NMR coil and n is the indexof the frequency generator.

This method is nowadays well-known and used in many NMR devices;however, the following key differences to prior-art methods aresuggested:

all generators v _(n)(t), n=1, . . . , N are fully correlated to eachother, i.e. at any time the frequencies of all generated signals havefixed ratios with one another.  (f19)

Here, it is sufficient to consider only one input signal s4 (FIG. 3), sothat L=1, and only one experiment, so that J=1. Therefore, the 1 and jindexes are dropped from u_(lnj)(t) and it becomes represented asu_(n)(t), n=1, . . . , N.

Consider that the input NMR signal is disturbed because an unstablemagnetic field and unstable oscillator are used. In this case, thissignal can be written as the following form:

${{f(t)} = {\sum\limits_{n = 1}^{N}\; {{Re}( {e^{{{iW}_{n}t} + {{iW}_{n}{\sigma {(t)}}} + {i{\overset{\sim}{\sigma}{(t)}}}}{{pn}(t)}} )}}},$

where σ(t) refers to the function of the unstable magnetic field, and{tilde over (σ)}(t) refers to the function of the unstable oscillator.In this case u_(n)(t) reads as:

u _(n)(t)=r _(n)(t)e ^(iθ) ^(n) (t)+iw _(n)σ(t)+i{tilde over (σ)}(t)

so that r_(n)(t) can be easily computed as r_(n)(t)=|u_(n)(t)|.

Some important considerations should be taken into account:

-   -   affordable unstable oscillators do have local stability and are        stable for a short period of time (several microseconds and        less); however, they may be unstable over longer periods        (several milliseconds and more);    -   in normal laboratory or industrial conditions, a magnetic field        does not fluctuate with high deltas, which only occur in an        exceptional cases like close proximity to electromotors,        electromagnets, high current switchers, etc; said magnetic field        can be stable for a short period of time (several microseconds        and less), but it may be unstable over longer periods (several        milliseconds and more).

Hence, σ(t) and {tilde over (σ)}(t) are considered as either piece-wiseconstant or piece-wise linear functions that cover said short-periodtime stabilities of oscillators and magnetic field.

Let us divide u_(n)(t) and r_(n)(t), defined on t=[0, T], into severalpieces τ=1, . . . , Ψ equal in time as:

${{{\overset{\sim}{u}}_{n\; \tau}(t)} = {{- i}\; \ln \frac{u_{n}( {t + {\frac{T}{\Psi}( {\tau - 1} )}} )}{r_{n}( {t + {\frac{T}{\Psi}( {\tau - 1} )}} )}}},{t \in \lbrack {0,\frac{T}{\Psi}} \rbrack},{\tau = 1},\ldots \mspace{14mu},\Psi,\mspace{14mu} {n = 1},\ldots \mspace{14mu},{N.}$

According to the assumptions of the piece-wise constants σ(t) and {tildeover (σ)}(t), it is sufficient to approximate ũ_(nτ)(t) asθ_(nτ)(t)+W_(n)σ_(τ)+{tilde over (τ)}_(τ). Usually the signal θ_(nτ)(t)itself is overdetermined and can be adequately approximated by themethod of model order reduction as is, for example, described inJaravine and Ibragimov 2006.

Hence, θ_(nτ)(t) is a three-dimensional object formed from n, τ, and tdimensions with low rank that may be represented as:

$\begin{matrix}{{{\theta_{n\; \tau}(t)} = {\sum\limits_{r = 1}^{R}\; {\theta_{nr}^{(1)}\theta_{\tau \; r}^{(2)}{\theta_{r}^{(3)}(t)}}}},{t \in \lbrack {0,\frac{T}{\Psi}} \rbrack},{\tau = 1},\ldots \mspace{14mu},\Psi,\mspace{14mu} {n = 1},\ldots \mspace{14mu},{N.}} & ({f20})\end{matrix}$

with small r compared to N and/or Ψ, and which can be found by solutionof one of the following minimization problems, either:

${\min\limits_{R,{\theta_{nr}^{(1)}\theta_{\tau \; r}^{(2)}{\theta_{r}^{(3)}{(t)}}},\sigma_{\tau},{\overset{\sim}{\sigma}}_{\tau}}{\sum\limits_{n = 1}^{N}\; {\sum\limits_{\tau = 1}^{\Psi}\; {\int_{0}^{T/\Psi}{{{{{\overset{\sim}{u}}_{n\; \tau}(t)} - {\sum\limits_{r = 1}^{R}\; {\theta_{nr}^{(1)}\theta_{\tau \; r}^{(2)}{\theta_{r}^{(3)}(t)}}} - {W_{n}\sigma_{\tau}} - {\overset{\sim}{\sigma}}_{\tau}}}_{2}^{2}{dt}}}}}},\ {{{or}{\theta_{n\; \tau}(t)}} = {{{\overset{\sim}{u}}_{n\; \tau}(t)} - {W_{n}\sigma_{\tau}} + {\overset{\sim}{\sigma}}_{\tau}}},{{where}\mspace{14mu} {\min\limits_{\sigma_{\tau},{\overset{\sim}{\sigma}}_{\tau}}{\int_{0}^{T/\Psi}{{{{{\overset{\sim}{u}}_{n\; \tau}(t)} - {W_{n}\sigma_{\tau}} - {\overset{\sim}{\sigma}}_{\tau}}}_{2}^{2}{{dt}.}}}}}$

Both minimization problems can be solved by the algorithm from Appendix2 or by any other method that will find the tensor decomposition of amultidimensional (≥3) object.

A similar method can be applied in the event of using a piece-wiselinear approximation instead of the piece-wise constants for σ(t) and{tilde over (σ)}(t). This approximation leads to

                                          (f21)${\min\limits_{R,{\theta_{nr}^{(1)}\theta_{\tau \; r}^{(2)}{\theta_{r}^{(3)}{(t)}}},\sigma_{\tau},{\overset{\sim}{\sigma}}_{\tau}}{\sum\limits_{n = 1}^{N}\; {\sum\limits_{\tau = 1}^{\Psi}\; {\int_{0}^{T/\Psi}{{\begin{matrix}{{{\overset{\sim}{u}}_{n\; \tau}(t)} - {\sum\limits_{r = 1}^{R}\; {\theta_{nr}^{(1)}\theta_{\tau \; r}^{(2)}\theta_{r}^{(3)}(t)}} -} \\{{W_{n}\sigma_{\tau}{\mathrm{\Upsilon}_{\tau}(t)}} - {{\overset{\sim}{\sigma}}_{\tau}{\mathrm{\Upsilon}_{\tau}(t)}}}\end{matrix}}_{2}^{2}{dt}}}}}},\mspace{20mu} {{{or}\mspace{14mu} {\theta_{n\; \tau}(t)}} = {{{\overset{\sim}{u}}_{n\; \tau}(t)} - {W_{n}\sigma_{\tau}{\mathrm{\Upsilon}_{\tau}(t)}} + {{\overset{\sim}{\sigma}}_{\tau}{\mathrm{\Upsilon}_{\tau}(t)}}}},{{where}\mspace{20mu} {\min\limits_{\sigma_{\tau},{\overset{\sim}{\sigma}}_{\tau}}{\int_{0}^{T/\Psi}{{{{{\overset{\sim}{u}}_{n\; \tau}(t)} - {W_{n}\sigma_{\tau}{\mathrm{\Upsilon}_{\tau}(t)}} - {{\overset{\sim}{\sigma}}_{\tau}{\mathrm{\Upsilon}_{\tau}(t)}}}}_{2}^{2}{dt}}}}},{{{where}\mspace{20mu} {\mathrm{\Upsilon}_{\tau}(t)}} = \{ \begin{matrix}{t \in {\lbrack {{( {\tau - 1} )\frac{T}{\Psi}},{\tau \frac{T}{\Psi}}} \rbrack \text{:}}} & {{1 + t},} \\{t \in {\lbrack {{\tau \frac{T}{\Psi}},{( {\tau + 1} )\frac{T}{\Psi}}} \rbrack \text{:}}} & {{1 - t},} \\{{otherwise}\text{:}} & 0.\end{matrix} }$

Hence, we have demonstrated how to stabilize NMR data acquisition andobtain pure spectra that are not disturbed by an unstable magnetic fieldand/or unstable oscillator.

This condition (f19) is sufficient for performing NMR signal processingin a fluctuating magnetic field and/or fluctuating oscillator; however,several additional conditions may improve results and/or be useful forparticular cases.

Said conditions may be one of the following: either

at least two repetitions of data acquisition should be performed,or  (f22)

two or more magnetic fields with different strengths should be situatedclose to one another and cover the measuring unit together with severaltransmitter and receiver coils, or coils,  (f23)

at least one non-zero-spin isotope with a priori known spectra should beeither:  (f24)

-   -   situated in the measured substance, or    -   incorporated as the reference unit inside one or several input        coils, or    -   incorporated in the walls of the measuring NMR camera.

Consider the first condition (f22): at least two repetitions of dataacquisition should be performed.

Here, the j-th index in u_(lnj)(t), j=1, . . . , J refers to the numberof experiments that are collected in different time-slots, as isdemonstrated in FIG. 4. The total number of input coils workingsimultaneously may be one or more, so we drop the index 1 fromu_(nj)(t), j=1, . . . , J, n=1, . . . , N.

This gives the construction,

n _(nj)(t)=r _(nj)(t)e ^(iθ) ^(n) (t)+iW _(nσj)(t)+i{tilde over (σ)}_(j)(t),

where σ_(j)(t) refers to functions of the unstable magnetic field and{tilde over (σ)}_(j)(t)—to functions of the unstable oscillator forevery particular j-th experiment.

As above, r_(nj)(t)=|u_(nj)(t)|. Assuming

${{{\overset{\sim}{u}}_{nj}(t)} = {{- i}\; \ln \frac{u_{nj}(t)}{r_{nj}(t)}}},$

then θ_(n)(t), n=1, . . . , N are computed according to the minimizationof:

$\min\limits_{{\sigma_{j}{(t)}},{{\overset{\sim}{\sigma}}_{j}{(t)}},{\theta_{n}{(t)}}}{\sum\limits_{n = 1}^{N}\; {\sum\limits_{j = 1}^{J}\; {{{{\overset{\sim}{u}}_{nj}(t)} - {\theta_{n}(t)} - {W_{n}{\sigma_{j}(t)}} - {{\overset{\sim}{\sigma}}_{j}(t)}}}_{2}^{2}}}$

so that

θ n  ( t ) = 1 J  ∑ j = 1 J   u ~ nj  ( t ) - 0  ( t )  ( 2  Wn - 3 ) + 1  ( t )  ( 2 - NW n ) 2 2 - 3  N ,

where

0  ( t ) = 1 J  ∑ j = 1 J   ∑ n = 1 N   u ~ nj  ( t ) , 1  ( t )= 1 J  ∑ j = 1 J   ∑ n = 1 N   u ~ nj  ( t )  W n ,  2 = ∑ n = 1N   W n , 3 = ∑ n = 1 N   W n 2 .

Hence, we demonstrate that if

-   -   all generators v_(n)(t), n=1, . . . , N are fully correlated,        i.e. at any time the frequencies of all generated signals have        fixed ratios to one another, and    -   at least two repetitions of data acquisition are performed,        there is a straightforward method for obtaining pure spectra        that are not disturbed by the unstable magnetic field and/or        unstable oscillator.

Consider the second condition (f23). In the event a focused magneticfield is constructed (like in FIGS. 14-18, 24-25) it is easy to performan experiment where two or more volumes with the substance to bemeasured are situated in magnetic fields of different strengths. Usingtwo or more transmitter and receiver coils, or appropriately focusingthe transmitting energy using the ELMATHRON beam, one can collect two ormore spectra of the same isotope (for example H) of the same substanceat two or more different magnetic field strengths. Doing so leads to twoor more different carrier frequencies being simultaneously measured, andfluctuations in time of the magnetic field and oscillator remain thesame for all these simultaneous measurements.

There are two cases possible with this scenario.

If the magnetic field strength differs in order by no more than severalpercent, then spectra (if excited similarly) can be scaled by thefrequency and will be identical. Two such spectra can be used tosubtract out oscillator instability.  (f25)

If the magnetic field strength differs considerably, or if the spectraare generated by different excitation sequences, then they cannot beconsidered identical; however, if one collects more than two suchspectra, they may be approximated with a low rank approximation becausethe main parts remain similar (dependent on chemical shifts) and whatdiffers is dependent on J-coupling.  (f26)

Case (f25) has a unique solution if either at least one referenceisotope is available or at least two measurements are performed. To findthis solution, one needs to outline a minimization problem similar to(f21) and use similar solution methods.

Case (f26) can also be solved with a very similar approach. Letu_(kn)(t), where k=1, . . . , K≥2 refers to the index of differentmagnetic field strengths and/or an excitation pulse sequence experiment.Since spectra for different excitations differ only in the J-couplingpart, it is clear that these spectra build a low rank object and,together with the n variable (isotope number), build a three-dimensionalobject similar to (f20) with minimization problem similar to (f21) andfor which similar solution methods can be used.

Now consider the third condition (f24): the situation with referenceisotope(s). In this case, just one measurement should suffice, so wedrop the index j from u_(ljn)(t).

Here the following minimization problem should be solved:

${\min\limits_{{\sigma {(t)}},{\overset{\sim}{\sigma}{(t)}},{p{(t)}}}{{{u_{\ln}(t)} - {e^{{{iW}_{n}{\sigma {(t)}}} + {i\; {\overset{\sim}{\sigma}{(t)}}}}( {{p_{n}(t)} + {q_{\ln}(t)}} )}}}_{v}^{v}},$

in any ν-norm ∥.∥_(ν), with 1≤ν≤∞, and where p_(ln)(t) are the referencespectra.

This minimization problem has unique solutions in the following cases:

-   -   L=1, p₁(t)=0, g₁₁(t)≠0, either σ(t)=0 or {tilde over (σ)}(t)=0        we need to perform one measurement on one coil, need only one        reference isotope, and need no such isotope in the measured        substance in case either oscillator or magnetic field is        unstable; the solutions are:

${{\overset{\sim}{\sigma}(t)} = {{0\text{:}\mspace{14mu} {\forall n}} = 2}},\ldots \mspace{14mu},{{N\text{:}\mspace{14mu} {p_{n}(t)}} = {( \frac{q_{11}(t)}{u_{11}(t)} )^{W_{n}/W_{1}}{u_{1\; n}(t)}}},{{\sigma (t)} = {{0\text{:}\mspace{14mu} {\forall n}} = 2}},\ldots \mspace{14mu},{{N\text{:}\mspace{14mu} {p_{n}(t)}} = {( \frac{q_{11}(t)}{u_{11}(t)} ){u_{1\; n}(t)}}},$

-   -   L=1, p₁(t)=0, g₁₁(t)≠0, p₂(t)=0, q₁₂(t)≠0 we need to perform        only one measurement on one coil, need only two reference        isotopes, and need no such isotopes in the measured substance;        the solution reads as:

${{\forall n} = 3},\ldots \mspace{14mu},{{N\text{:}\mspace{14mu} {p_{n}(t)}} = {{u_{n}(t)}( \frac{u_{1}(t)}{q_{1}(t)} )^{k}( \frac{u_{2}(t)}{q_{2}(t)} )^{1 - k}}},{k = \frac{W_{n} - W_{2}}{W_{1} - W_{2}}},$

-   -   L>1:

${{p_{n}(t)} = \frac{{{q_{l_{1}n}(t)}{u_{l_{2}n}(t)}} - {{q_{l_{2}n}(t)}{u_{l_{1}n}(t)}}}{{u_{l_{1}n}(t)} - {u_{l_{2}n}(t)}}},{l_{1} \neq {l_{2}.}}$

Every signal in f, v, and u in the described method may be analog ordigital. At any point between blocks s3, s4, s5, s10, s11, s12, s13, ands14, one or several analog to digital converters (ADCs) and/or one orseveral digital to analog converters (DACs) can be incorporated toconvert between signal types. Any of the blocks s3, s10, s11, s12, ands13 can be implemented through analog and/or digital means. In eachparticular case, the use of digital, analog, or a mix of digital andanalog signals is dependent upon component counts, costs, desiredaccuracy, average signal frequency, and many other factors.

In the output of s3 at FIG. 3, |u_(ln)(t)| refers to r_(ln)(t) and isweakly dependent on fluctuations in the permanent magnetic field andoscillator. It is generated with several microsecond delays after theinitial signal appears, so all real-time methods that require only r maybe used.

Usage of internal marker(s) for one isotope or a spectrum that may bematched by internal database, together with correlated oscillators,gives a straightforward way to get absolute spectra for all othermeasured non-zero-spin isotopes without the usage of standard substanceslike tetramethylsilane for 1H, 13C, or 29Si. Indeed, if we know orcompute a spectrum for one non-zero-spin nuclei type so that it isscaled to known standard (i.e. we have absolute spectra), and we knowthe exact relation between NMR isotopes and use this relation on thecorrelated oscillators, all other spectra are already absolute spectra.This is a very important feature for inorganic or element-organicchemistry, since most non-zero-spin isotopes have few response lines intheir spectra and cannot be matched without usage of chemical standards.

Hence, we demonstrated that correlated oscillators allow the removal ofinstability in the magnetic field and/or oscillators. This capabilityopens a new horizon for the use of small and affordable magnets, magnetswith Halbach-like focusing of the magnetic field, and affordableoscillators.

The ELMATHRON

The Electron Larmor Microwave Amplifier THReaded On Nuclei (ELMATHRON)is an apparatus to deliver electron Larmor frequency waves whoseamplitude is modulated by a nuclear Larmor frequency pulse. An exampleof the waveform is found in FIG. 11, where a highly oscillated signal(ca. 40 GHz at 1.5 T) that refers to the Larmor frequency of electronsis amplitude modulated by the low oscillated signal or pulse referringto the Larmor frequency of nuclei (ca. 60 MHz for 1H at 1.5 T).

The ELMATHRON (FIG. 10) consists of a hermetically-sealed, deepvacuum-compatible glass or ceramic vessel e2. All energy transmissionsinto the ELMATHRON occur by inductive and/or electromagnetic methods.

A glass, ceramic, or any high voltage-resistant tube e9 is situatedinside the vessel e2 and may have a printed metallic or conductivedesign (e5, e6, e7, e11, e16) on its inner and outer surfaces.

The bottom of the tube e9 contains the secondary winding e16 of aforward converter. The primary winding e17 of the forward converter issituated outside of the hermetically-sealed vessel e2 and is organizedby many parallel windings. Each has a few turns that are operated at lowvoltage (5-100 V) so that the voltage/turn ratio is about 2-100 V. Incontrast, the secondary winding e16 has a large number of turns. If thesecondary winding contains printed coils in the inner and outer sides ofthe tube e9, the total number of turns may be around 10,000, and thetotal voltage in the second winding of the forward converter may easilyreach 100 KV.

The ELMATHRON is designed to sustain a deep vacuum for a long period oftime. For this reason, the following components are used:

-   -   glass or ceramics parts e2, suitable for deep vacuum,    -   printed traces of copper, silver, aluminum, or other        vacuum-friendly metals and alloys in e5, e6, e7, e11, e16,    -   tungsten and high-melting metals in e1, e13, and    -   appropriate getters e3 and/or e15.

The printed coil e16 is connected on one side over the getter block e15to the cathode e13 of the ELMATHRON, and on the second side over tracese11, diffraction grating e7, and shielding screen e5 to the anode e6.Smooth turns in each trace on the conductive components, such as tracesbetween e11 and e16, will prevent unnecessary electromagneticinterference.

The anode e6 of the ELMATHRON is preferably printed/deposited on theinner side of the tube e9 with an additional metal e5 as a shield toprevent unnecessary electromagnetic interference. The electron beamflows from the cathode e13 to the anode e6. The permanent magneticfield, created by external magnets e10, causes electrons to movehelically in tight circles around the magnetic field lines as theytravel lengthwise through the tube. At the position in the tube at whichthe magnetic field reaches its maximum value, the electrons radiateelectromagnetic waves in a transverse direction (perpendicular to theaxis of the tube) at their Larmor (cyclotron) resonance frequency. Theradiation forms standing waves in the tube, which acts as an open-endedresonant cavity, and is formed into a beam that radiates through thediffraction grating e7.

A reflector e8 may be constructed as a cone, a flat mirror, afocusing/collecting mirror, or any of many other possible shapes suchthat some part of the emitted waves may be reflected back to the cathodee13 to accelerate the cathode's electron emission.

The cathode is preferably constructed as the shorted turn e13. It isimportant that the cathode be made of high-melting metals and remains ina high-temperature state during operation. Preferably, the cathode ismade in the form of a circle that is as large as possible while also nottouching the walls of e9.

The getter block e15 may be omitted, so that the cathode e13 is directlyconnected to the printed coil e16.

In the case of a getter block e15 being present, it may have arbitraryshape, with the following restrictions: the top face and its surface(that looks to the anode) should be as large as possible, and no shortedturns, which may result from inductive transformations from e14 and/ore17, are permitted.

Said getter e15 can be made as a metal foam block that completely fillsthis tube and has notches so that this foam does not build shortedturns; it can also be made as a flat spring or as any other form withmaximal possible surface area and no shorted turns.

It is important to make the connection from the cathode e13 with tinconductive metal wire(s) so that heat from the cathode is nottransferred to said getter e15; the getter should remain cold so that itcan function in collecting unnecessary ions and improving the vacuuminside the ELMATHRON.

The embodiment including said getter e15 improves the lifespan of thedevice. In this case, the ELMATHRON works as a sputter ion pumpmaintaining ultra-high vacuum for a long period of time. Ions situatedinside the ELMATHRON flow in the direction of the cathode and arecaptured by the cold getter e15.

The getter e15 can be made of titanium, a titanium-rich alloy, a Ti—Zr—Valloy, or any other conductive wire of appropriate alloy.

Making the getter e15 massive or using massive foam (several millimetersin height) improves cooling of its upper face, resulting in improved ionabsorption.

The external inductive heater e14, with its optical feedback e12 andcontrol unit e19, sustains the high-temperature state of the cathode.

One can use an electromagnetic beam e12 (a laser, for example) to heatthe cathode e13 in parallel with or alternatively to inductive heating;electromagnetic beam heating can also be used to bring the surface ofthe cathode into an excited state to improve the overall efficiency ofthe ELMATHRON's operation.

The first step of the working cycle of the forward converter createshigh voltage on the secondary winding e16, so that the cathode e13assumes a negative charge and the anode e6 assumes a positive charge,forcing the emission of electrons from the cathode to the anode. Thesecond step of the working cycle exchanges the polarity of chargesbetween cathode and anode, thereby locking the electron beam to thebackward direction.

When printed on the inner and outer side of the tube e9, the secondarywinding e16, diffraction grating e7, connections e5, e11, e15, and theanode e6 may be organized as a thin metallic film that is chemicallydeposited or sprayed.

The spaces between traces are preferably burned/etched by theoptical/laser heater, so that a 1-100 μm thin layer with 1-10 μm oftrace deviation accuracy is afforded during production.

Having the thin layer on the printed coil e16 with a total length of 10cm may provide a pulse-width of less than 10 ns with 1000 V/ns and 10⁵watts of peak power at the coil. Parameters even better than this may beachieved.

Due to its construction, the working cycle of the forward converter maybe as brief as several nanoseconds and may be chosen to match theduration of the excitation NMR pulse sequence, during which each pulseis modulated with the electron Larmor frequency. Hence, the ELMATHRONworks as a polarizer (on the electron Larmor frequency), as an NMRtransmitter (on the nuclear Larmor frequency), and as a phased-arraytransmitter (taking the diffraction grating into consideration and/orseveral ELMATHRON vessels working in parallel).

It is evident that instead of the forward converter scheme, it ispossible to use full-bridge, half-bridge, and many other similartransformer schemes. However, the forward converter maximally reducesthe total count of components and appears to be optimal for the outlinedgoal—providing a dual-band Larmor electron and nuclei frequencygenerator.

Magnets

Since the magnitude of the electric response from an NMR experimentgrows quadratically with regard to the magnetic field strength used, itis important to use magnets with the highest possible field strength. Asdiscussed previously, the magnets may be either:

-   -   an external magnetic source as, for example, is disclosed in        FIG. 18, or    -   embedded permanent magnets as, for example, are disclosed in        FIGS. 13-17, 20.

In the case of embedded permanent magnets being used, they may haveeither:

-   -   anisotropic magnetization, where the entire magnet(s) are        magnetized in one direction (FIGS. 21A, 22 and 23), or    -   well-known Halbach structure or any other similar structure        where the magnetic field in the predetermined zone may be larger        (often by several times) than could be achieved with anisotropic        magnetization.

Nowadays, Halbach structures are often used in NMR spectrometry;however, they always require joining many small magnetic parts.

In the case of one transmitter and receiver coil assembly (FIG. 12)being used, the optimal Halbach magnetization occurs as in FIG. 24.

In the case of an ELMATHRON with several coil receivers (FIGS. 14-18)being used, the optimal Halbach magnetization may be even morecomplicated, as shown in FIG. 25. Here, the direction of the magneticfield in the receiving coils is anti-parallel to the direction of themagnetic field in the ELMATHRON vessel.

In the case where such an array is constructed with several pieces ofmagnets, one needs to combine an enormous number of magnetized pieces;doing so may be commercially ineffective.

In the case of MR. NIB technology (FIG. 20) being used, the optimalHalbach magnetization may be even more complicated and looks as in FIG.21B. The key advantage of this method is to generate an extremal (highor low) magnetic field strength on a point situated far from themagnets, and to not have any such extremal magnetic strength anywhere inthe neighborhood of this point or in the area where the patient's bodymay be situated. This result is achieved simply by appropriatemagnetization of the magnets. A representative contour plot of magneticfield strength sandwiched between these magnets is given in FIG. 21B.

In addition, the combination of a modulated ELMATHRON beam, magneticfield, and appropriate non-zero-spin isotope opens the new possibilityof using an electromagnetic field of nuclear Larmor frequency on saidnon-zero-spin isotope instead of or in parallel with said modulatedELMATHRON's beam.

Hence, the key advantage compared to U.S. Pat. No. 8,148,988 consists ofthe direct magnetization of magnetic material during magnetpressing/sintering/casting/forming, either

-   -   1. to achieve a field strength outside the magnets that is        higher than the maximal possible field strength of anisotropic        magnets for the same material, or    -   2. to produce a local extremum of magnetic field strength (this        case is mainly useful with MR. NIB technology).

Consider making each magnet of the ELEGANT NMR and MR. NIB technologies,i.e. every g7, g8, g9, g10, g11, and g12, independently as cylinders or,in general, as any arbitrary shape. It is easy to predict by numericalcomputation an optimal magnetization for each point of these magnetsthat yields the maximal possible magnetic field strength in a measuredarea outside of the magnet itself. In the embodiments comprisingELMATHRON(s), said maximal possible magnetic field strength should be inthe measured area and inside the ELMATHRON's vessel. There are twovariants with parallel and anti-parallel magnetic fields in saidmeasured area and ELMATHRON vessel. Both variants work well, and whichvariant should be used depends on the device and magnet sizes.

Hence, distribution of the anisotropy of magnetic particles inside themagnets should be as in FIGS. 21B, 24-27, and this magnetization shouldprovide the maximal possible magnetic field in the desired area.

The optimal magnetization of magnets g11 and g12 is highly dependent ondevice size, the set of non-zero-spin isotopes used for MR. NIB therapy,and the general requirement to generate an extremum of magnetic fieldstrength, so many different magnetizations may be suitable.

Nowadays, there are two main technologies for permanent magnetconstruction:

-   -   forming magnets from powder, and    -   casting magnets.

Both technologies require a permanent magnetic field to be appliedduring forming or casting, and after this procedure, one needs tomagnetize the magnet.

Formation of a magnet may be realized through many methods: by pressure,by additional lubricant and/or glue, by sintering pressed powder, etc.In all cases, it usually involves additional pressure being applied tothe powder, and may require postprocessing (heating/sintering, etc)after this procedure.

Casting a magnet requires liquid magnetic material at high temperature,and that the material is crystallized in an external magnetic fieldduring cooling.

In this patent application, we proposed to apply a non-uniform magneticfield of special shape during casting or forming.

Consider first the forming of magnets from anisotropic magnetic powder.

To make such a magnet, the following method and corresponding apparatus(FIG. 29) is suggested. It is comprised of

-   -   a molding matrix g19,    -   a molding tool g18,    -   a set of one or several magnetic field creating and adjusting        materials g21:        -   permanent magnets, and/or        -   ferromagnetic materials, and/or        -   permanent electromagnets, and/or        -   superconductor electromagnets, and/or        -   any other non-magnetic materials, and/or        -   permanent magnet(s) previously manufactured with the same            technology, and    -   a magnetic powder g20 with particles that can be anisotropically        magnetized. whereby    -   said magnetic powder is situated in said molding matrix,    -   said molding tool acts on said magnetic powder, reducing its        volume and forming a molded magnet, and    -   said magnetic field creating and adjusting materials are        situated in a predetermined spatial configuration.

To predict said predetermined spatial configuration, one needs to use awell-known equation that computes the magnetic field in a point Yϵ

³ occurring from a magnetic dipole situated at a point Xϵ

³ with its magnetization direction Mϵ

³:

$\begin{matrix}{{{B( {\overset{\_}{M},X,Y} )} = \frac{{3( {Y - X} )( {Y - X} )^{T}\overset{\_}{M}} - {{\overset{\_}{M}( {Y - X} )}^{T}( {Y - X} )}}{{{Y - X}}_{2}^{5}}},} & ({f27})\end{matrix}$

and performs the following algorithm.

ALGORITHM Nr. 3.

-   -   1. perform finite element discretization of the complete area        where the molded magnet is being pressed,    -   2. for the spatial distribution of every permanent magnet and/or        permanent electromagnet,        -   3. find the numerically appropriate magnetization direction            for every said finite element, checking that discretization            in that finite element is fine enough to achieve a smooth            and accurate solution,        -   4. take each finite element and scale the magnetic field in            such a way that it is maximally magnetized,        -   5. compute with the help of (f27) a magnetic field from the            all finite elements in            -   6. the measured area; and            -   7. if needed, the ELMATHRON's vessel;            -   8. the area of the patient's body where MR. NIB therapy                is to be used,    -   9. perform steps 3-8 maximizing/optimizing the magnetic field in        the desired area; if needed, constrain divergence of the field        in that area; and find the best possible configuration of        permanent magnets and/or permanent electromagnets.

Said algorithm delivers the optimal configuration of permanent magnetsand/or permanent electromagnets and, if a sintering device FIG. 29 isconstructed according to these rules, the magnetic field of the pressedmagnet will be as large as possible with respect to magnet size anddesired area and constraints in magnetic field divergence.

Additional fluids, and/or ultrasound, and/or shaking of the area g20 maybe helpful, because adding fluid will make Bingham fluids from thispowder and allow the rotation of magnetic particles with less externalmagnetic flux, while ultrasounding and/or shaking improve thetransformation of this mixture into Bingham fluid.

Hence, magnet production can be performed by the following steps:

1. Based on physical shapes and numerical simulations, choose theappropriate geometry of magnet g20 and area g21 with

-   -   permanent magnets, and/or    -   ferromagnetic materials, and/or    -   permanent electromagnets, and/or    -   superconductor electromagnets, and/or    -   any other non-magnetic materials, and/or    -   permanent magnet(s) previously manufactured with the same        technology.

2. Insert magnetic powder with/without fluids into the area g20,

3. Slowly apply pressure from g18 to perform pressing and, in parallelto this procedure, apply shaking and/or ultrasonic vibration. At thefirst stage, a constant pressure should be applied based on the shapeand size of the magnetic powder. During this stage, magnetic particlesmay rotate to situate themselves in the direction of the externalmagnetic field organized by g21. When the volume of the magnet g20 hasbecome less than the possible volume where each average particle touchesits neighbors, the pressure should be slowly increased until coldsintering occurs.

4. The constructed magnetic part is then sintered according to theappropriate process for its material. During sintering, the magnetusually loses its magnetic power; however, it becomes stable withphysical stress since all magnetic particles become fixed.

5. The constructed part is next inserted into a device FIG. 30 that issimilar to that used in stages 1-3; however, instead of permanentmagnets/electromagnets, a pulse magnet(s) g22 that may achieve a pulsemagnetic field of several Tesla with similar magnetic fieldconfiguration is situated in the area g25, and a short electromagneticpulse is applied so that the magnet becomes magnetized.

Hence, this method allows making a magnet such that it will producehigher magnetic strength outside of its shape than if it were a largeanisotropic magnet constructed from the same magnetic material. As anexample, we were able to achieve a magnetic field of 2 T for magnets of24 mm diameter and FIG. 25 shape with material that can deliver atmaximum 1 T in an anisotropic version.

Magnet casting may be performed with similar technology; however,instead of applying pressure to the magnetic powder, we should applyheating.

The key idea in this case is to use the same electromagnetic coilsand/or materials to generate the external magnetic field and to produceheat. Heating may be organized by:

-   -   resistive heating of one or several coils, and/or    -   inductive heating of casted material, and/or    -   inductive heating of conductive crucible with casted material,        and/or    -   resistive heating of casted material.

Hence, magnet production can be realized through the following steps:

1. Based on physical shapes and numerical simulations, choose theappropriate geometry of magnet g20 and area g21 with

-   -   permanent magnets, and/or    -   ferromagnetic materials, and/or    -   permanent electromagnets, and/or    -   superconductor electromagnets, and/or    -   any other non-magnetic materials, and/or    -   permanent magnet(s) previously manufactured with the same        technology.

2. Insert magnetic material for casting into the area g30,

3. Switch on heating so that said magnetic material melts.

4. After the magnetic material is melted, switch off inductive heating(if it was used) and switch on the electromagnets on a level such thatthey produce a magnetic field.

5. By controlling the cooling of electromagnets and resistive heaters,with/without the help of additional temperature sensors, perform slowcooling of said magnetic material while keeping the magnetic field at alevel that is sufficient to cast an anisotropically-oriented magneticstructure.

6. When the crystalline structure of casted magnetic material is frozenand the magnetic material is below its Kuri point, one should apply apulse magnetic field of several Tesla with similar magnetic fieldconfiguration as was used during casting, so that the magnet becomesmagnetized.

Hence, this method also allows making a magnet such that it will producea higher magnetic strength outside of its shape than if it was a largeanisotropic magnet constructed with the same magnetic material. As anexample, we were able to achieve 3 T for magnets of 24 mm diameter andFIG. 24 shape with material that can deliver at maximum 1.4 T in ananisotropic version.

In-situ portable spectrometers, based on ELEGANT NMR with and withoutELMATHRON, are preferably constructed with small magnets. These magnetsmay lose their magnetic strength over time because they can bedemagnetized when placed in inappropriate conditions, e.g. nearelectromagnets or large iron parts. To extend their working lives thedevice of FIG. 30 or a variant of FIG. 31 without heating may be used torecover depleted magnets.

Magnetic Material

Nowadays, there are many magnetic materials available for magnetconstruction by either sintered or casted processes;

-   -   sintered magnets may contain Nd—Fe—B, Sm—Co, Al—Ni—Co—Fe, Mn—Bi,        Mn—Al, and many other alloys, while    -   casted magnets contain mainly Al—Ni—Co—Fe alloys.

If casted, the magnetic material should be placed at high temperatureand slowly cooled. Doing so requires that the casted material be held informs resistant to high temperature.

If sintered, the magnetic material should be placed on a close form andadditional pressure applied. This requires that materials resistant tohigh pressure to be used to hold the sintered material.

The construction process requires an external magnetic field. To createa permanent magnetic field with anisotropy over a large region, one canuse Helmholtz coils. In this case, the area with high magnetic fieldstrength and anisotropy is situated physically far from the area wheremagnets are casted or sintered. Hence, there is no difficulty in placingthe forms for casting or sintering far away from the electromagneticcoils that generate the permanent magnetic field.

The typical permanent magnetic field is sourced from copper coils, whichare not very resistant to a high-pressure environment. The typicalpressure for synthesizing sintered magnets is above 3000 bar;withstanding this requires the enclosure for this process to beconstructed precisely. For some magnetic materials that sinter at veryhigh pressure (above 5000 bar), making copper coils that can withstandthat pressure may be almost impossible.

Similar difficulties complicate the casting of Halbach-like structureshere, one should place a permanent magnetic field source very close tothe casted material while it is at high temperature. The typical coppercoils do not withstand temperatures above 1000° C., and at elevatedtemperatures additionally have their electric conductivity reducedsix-fold. It is thus necessary to provide a good thermal barrier betweenthe coils and the casted material, or else to find an alternative fieldsource material for magnet production.

For the magnet being constructed, alloys of Al—Ni—Co—Fe are verypromising materials in both casted and sintered processes because theyare capable of achieving 1.4 T of residual magnetization as anisotropicmagnets. These alloys consist of two independent magnetic crystals:CoFe₂ crystals with high coercivity and magnetic field strength, andAl—Ni crystals which have poor magnetic properties but allow thebuilding of the so-called matrix, where the CoFe₂ crystals freeze duringcasting.

However, these alloys have very high temperatures of casting (from 700°C. to 1100° C.), which restricts their use in the casting ofHalbach-like structures. Furthermore, sintering these alloys requiresenormous pressure (above 4000 bar), which also restricts their usage insintered Halbach structures.

We suggest the substitution of AlNi crystals in Al—Ni—Co—Fe alloys withother magnetic materials that have lower melting temperature and/or lessresistance to high pressure. A good candidate would be the well-studiedMnBi crystals that, when more Bi is incorporated, can be melted attemperatures as low as 400° C. Any other low-temperature andlow-viscosity magnetic material can be also used, for example MnAlalloys.

As a good example of magnetic material for Halbach casting, we suggest amixture of CoFe (or SmCo) crystals, MnBi alloy, and Bi (and/or In) withmolar ratio of 1:1:1/4 or similar. The CoFe crystals are the main phaseof Al—Ni—Co—Fe magnets and have a body-centered cubic (BCC) structure.One can increase the molar ratio of CoFe up to three to obtain aslightly stronger magnet at the cost of requiring higher temperature forcasting. If the molar ratio of CoFe is below one, the magnet becomesweaker.

In addition to adjusting the relative molar ratio of CoFe, magnetproperties are affected by the alloy proportions; all Co_(x)Fe_(1-x),where xϵ[0.2, 0.8] form a BCC structure, were tested and can be used forthe production of magnetic material.

To make said magnetic material, we take Co, Fe, Mn, Bi, and In at amolar ratio of 1:2:1:1.1:0.27 and in the form of ultrafine powders (1-10um). These are placed in a vacuum chamber (10⁻⁴ Torr) and heated at 200°C. for about one day. After that, we increased the vacuum to 10⁻⁶ Torrfor several hours, sealed the chamber, and heated it to ca. 1500° C. foranother hour. It is important to seal the chamber because at thistemperature, bismuth evaporates with high pressure (ca. 1 bar) and Mnand other metals can immediately react with oxygen from the air. Wesuccessfully tested two different methods for heating, inductive andheat transfer. We expect that any other heating methods such asresistive or discharge should also work well. After said heating, weslowly (0.5° C. per minute) cooled the material to room temperature.

The following physical properties were observed: the mixture of powdersmelts at circa 1500° C. with a density of about 2.5-3 g/cm³, in contrastto a density at room temperature of about 7.5 g/cm³ (and ca. 5.5 g/cm³before sintering/casting). If the melting procedure described above isperformed, the obtained magnetic material solidifies at ca. 400° C. andliquifies at circa 900-1000° C. At temperatures of 200° C. and above,this magnetic material irreversibly reacts with oxygen from the air,completely losing its magnetic property. The magnetic material can bemilled to fine powder, and can be pressed and sintered at pressuresstarting from ca. 100 bar, with good results achieved below 1000 bars.In the case of casting in a magnetic field with this material, it ispossible to start casting at 450-500° C. with slow cooling (0.2° C. perminute) to 300° C.

The key difference of this prepared magnetic material (FIG. 28) fromcommonly-used materials is that it builds BCC Co_(x)Fe_(1-x) crystalsg32 that are situated on another material (low temperature meltingalloys g34 including one or several elements of In, Bi, Sn, Ga, Tl, Cd,Zn, Pb, Te, and/or ferromagnetic like Mn—Bi g33). This combination givesnew mechanical, thermal, and magnetic properties, i.e. the achievedmaterial

-   -   can be sintered at low pressure (1000 bar),    -   can be casted at low temperature (500° C. and below),        and is perfectly suitable for a Halbach-like sintering/casting        process as proposed in our patent application.

Hence, said magnetic material used in said magnet sintering/castingprocess makes possible the affordable production of small magnets thatfocus a magnetic field to very high levels, allowing a field strengththat is several times larger than the currently available 1.4 T magnets.

MR. NIB

Magnetic Resonance Non-Invasive Blade and Magnetic ResonanceNon-Invasive Beam (MR. NIB) is the proposed method of this patentapplication for non-invasive tissue ablation using heat generated by NMRand/or DNP-NMR without the need to invade the body with probe(s). Itemploys a non-uniform permanent magnetic field (NUPMF) n6 (FIG. 20) withan appropriately sized gradient of magnetic field inside the patient'sbody.

The interaction of a permanent magnetic field and an alternate magneticfield (AMF) without DNP and/or without magnetic field focusing is wellknown, but never used for ablation or heating of tissues because themethod has poor spatial accuracy. This poor spatial accuracy resultsfrom to the low frequency waves involved in AMF (100 MHz and less),which are several meters in length and cannot be accurately focused onthe intersection of the permanent magnetic field and AMF.

MR. NIB will direct the NMR device to generate a NUPMF of predeterminedshape n6 via several permanent or superconductor magnets n1 includingthe magnets proposed above to focus NUPMF; the movements of thesemagnets are controlled in real time from the MR. NIB computer appliance.Movement of the magnets provides a coarse magnetic field shape; finetuning/adjustment is performed by adjusting the (gradient) coils.

The fact that a permanent magnet assembly with focused permanentmagnetic field produces a high intensity magnetic field only over aregion of small size additionally improves the safety of this systemregarding possible accidents with magnetic parts during surgicaloperation and treatment.

Perpendicular to, or at least non-parallel to, the direction of theNUPMF, one or several transmitters of microwaves of Larmor electronfrequency with amplitude modulated AMF are controlled by block n5 tosupport mechanical movement in real time. The AMF is generated with apredetermined sequence of pulses in order to ensure that it will containone or several mixtures of predetermined frequencies. To ensure that thefocal point of the ablation is targeted to the tumor and/or ablatedtissue, and/or tissue for heating, the shape and focal point n7 of thealternate field can be changed in real time.

The patient body that is the object of the surgical procedure must beable to be physically situated within the physical MR. NIB components.Accordingly, a physical constraint that must be addressed in theconstruction of hardware is the need to ensure sufficient separationbetween magnets/transmitters and the patient's body, so that they do notcause discomfort to the patient during the treatment.

The key differences of this proposed non-invasive heating method are inits usage of a non-uniform permanent magnetic field that is focused onlyon the region intended for ablation/heating and/or the usage of dualband DNP-NMR systems as proposed above regarding ELMATHRONs.

As discussed previously, MR. NIB represents a fully non-invasive methodof heating and/or activation of pharmaceuticals for internal organs inhuman bodies. This property supports the surgeon in the performance ofsurgical operations using NMR energy without making any cuts in thebody. Hence, an accurate monitoring and visualization process isrequired for accurate guidance of the non-invasive, electronic “surgicalscalpel.” If used with a real-time database method (Algorithm Nr 2 ofthis patent application), MR. NIB provides an electronic and/or humansurgeon with that necessary real-time visualization, which can beleveraged to provide fully automatic, semi-automatic, or fully manualcontrol over the surgical procedure.

The key difference in the proposed visualization approach fromtraditional methods is the use of the real-time method discussed in thesection “real-time method of signals from repeating processing method,”which supports the creation and storage of an a priori interactive mapof the target surgical zone.

In the case where any receiver's response n2 does not match a previouslycollected response and its corresponding image, this method willautomatically and immediately switch the energy generation system offfor one or more time periods until synchronization of the receiver'sresponses to pre-stored images is achieved. Automatically turning offthe heating energy in this manner is necessary to ensure that theposition where the magnetic resonance “blade/scalpel” function is beingapplied is definitively established, and will avoid tissue destructionoccurring external to the target region. In parallel, a new image willbe computed for this new sensor data set and used to update thedatabase.

This electronic scalpel/blade can be automatically switched off in a fewmilliseconds and is controlled by dedicated computing resources. The MR.NIB method controls imaging and scalpel/heating operation at the sametime without any impact to other functions. If desired, the guidancecapability can be configured to use programmatic control of thetargeting functions, thereby supporting a fully automatic ablationprocedure.

Hence, the implementation of the MR. NIB method for guidance iscomprised of the following steps:

The method integrates several mechanically-controlled receiving antennas(n2 and n3) and requisite computing appliances to perform deterministicmatching and inverse solution of MRI calculations according to AlgorithmNr. 1. These components utilize an inverse Maxwell equation solver forthe generation of a visualization to support a surgeon's visualizationof the procedure and automatic/semiautomatic guidance of thenon-invasive blade.

An a priori database is constructed for an individual patient accordingto Algorithm Nr. 2 through a short (several minutes) mapping sessionprior to performance of the surgical scalpel procedure. Data collected,computed, and stored here for the intended ablation session providesrecallable information on every possible location of the target tumor,including effects and movement from patient activity such as breathing.The volume of data to be available for instant recall from conventionalNMR and/or MRI sensors is several dozen gigabytes per second, orapproximately 200 Tb in total for a two-hour ablation session.

The proposed real-time method, together with signal processing methodsdescribed in FIGS. 1-2, compresses this data to a few gigabytes ofmatrix factors, including a computational database made for everypossible magnet/adjusting coil/frequency combination, and makes itpossible to perform the guidance in real time and to drastically reducehardware expenses. An important feature of the MR. NIB approach lies inthe fact that its guiding function may also be applied with otherablation methods such as HIFU.

1: A real-time processing method to search for and perform real-timeactions comprising of: a. a first component, a real-time intermediatedata generator and sensor(s) s23; b. a second component, a non-real-timeaction generator s24; c. a third component, a non-real-time databaseupdater s25; and d. a fourth component, a real-time database searchers26, whereby e. said real-time actions are a series of predeterminedsequences to be performed by means of apparatus action and based onresponses from said sensor s23 such that the delay between physicalmatters appearing on said sensors and completion of said action isbounded by a predetermined constant; f. said first component measuresphysical and/or chemical properties of the investigated object anddelivers a real-time data set array z_(ϕ)(t) ϵ

^(N) ^(z) that characterizes said object with regards to its currentstage, chemical composition, and/or any other feature at eachpredetermined time step 0 that is a short period of time and isnegligible in comparison to said predetermined constant; g. said secondcomponent is implemented in an appliance unit that receives z_(ϕ) of theϕ-th time step and performs computations that transform this data setinto a control sequence yϕ that may be used later for real-time actionas said predetermined sequence; h. said second component is implementedin one or several appliance units that perform their work in paralleland deliver the results when the computations are ready; i. each newdata set arriving from said first component to said second component isallocated to the first freed appliance unit; j. if no free applianceunits are available, either said new data set is discarded, or one ofthe oldest computed data already running on appliance units is discardedand said new data set is allocated to this free appliance unit; k. saidthird component is implemented in an appliance unit that receives a pairof data sets z_(ϕ) and y_(ϕ) when both data sets are ready; l. saidappliance unit in said third component incorporates said pair of datasets into a database; m. said database which has already incorporateddata sets from the ϕ-th time step is abbreviated as D_(ϕ); n. saiddatabase must allow for the searching and finding of any data set withindeterministic real-time; o. said fourth component is implemented in anappliance unit that takes real-time data z_(ϕ) from said first componentand searches for z_(ϕ) in the currently available database; if it ismatched, a corresponding data set array y _(ϕ) is delivered in realtime. 2: The real-time method of claim 1 wherein that implements thefunctionality of a surgical robot, a. said surgical robot performsablations by the combination of b. a permanent magnetic field n6, withmechanical and/or electronic control of its shape; c. a microwavebeam(s) with non-zero-spin nuclei Larmor frequency corresponding to saidpermanent magnetic field n6, with mechanical and/or electronic control;and d. non-zero-spin nuclei that are available or/and intentionally madeavailable in ablating tissues. 3: The real-time method of claim 1wherein that implements the functionality of a surgical robot, a. saidsurgical robot performs ablations by means of high-intensity focusedultrasound. 4: The real-time method of claim 1 wherein that implementsthe functionality of a real-time switch to monitor a. a chemicalprocess, and/or b. a fluid chemical composition flowing in a measuredunit, and/or c. a spatially inhomogeneous chemical composition thatchanges its relative chemical distribution over a predetermined time,whereby d. said database learns according to provided samples ofmaterials and responses for each material, and e. a real-time responseoccurs if one or several chemical components achieve a predeterminedthreshold. 5: The real-time method of claim 1 wherein said database isconstructed as a low rank approximation of a matrix Z=[z₁, . . . , z_(ϕ)]ϵ

S_(B)×ϕ, where S_(B) is the total amount of discretized parameters oneach time step. 6: The real-time method of claim 1 wherein said databaseis constructed based on a support vector machine algorithm. 7: Thereal-time method of claim 1 wherein said database is constructed basedon a deep learning algorithm. 8: A non-invasive method: a. for ablationof tissues, b. for producing controlled heating, or c. for activation ofchemical reactions inside a body comprising of: d. a permanent magneticfield n6, with mechanical and/or electronic control of its shape; and e.a microwave beam(s) with non-zero-spin nuclei Larmor frequencycorresponding to said permanent magnetic field n6, with mechanicaland/or electronic control, whereby f. the intersection of g. saidpermanent magnetic field n6, h. said microwave beam(s) n7, and i.non-zero-spin nuclei refers to a target region. 9: The method of claim 8wherein said microwave beam(s) are modulated by the electron Larmorfrequency corresponding to said permanent magnetic field n6. 10: Themethod of claim 8 wherein said microwave beam(s) n7 with electron Larmorfrequency corresponding to said permanent magnetic field n6, which ismodulated by an amplitude of the Larmor frequency of non-zero-spinnuclei, and with which mechanical and/or electronic control are used.11: The method of claim 8 wherein said permanent magnetic field is madeusing permanent magnet(s) that have non-uniform magnetic polarizationsuch that the magnetic strength in the measured area is greater than themagnetic strength of an anisotropic magnet of the same material andsize. 12: The method of claim 8 wherein the intersection point isdetermined by an external program that provides 3D coordinates. 13: Themethod of claim 8 wherein the intersection point is determined by theoperator/surgeon who targets this point according to his or herknowledge. 14: The method of claim 8 wherein the intersection point isdetermined by a distribution of medicaments/pharmaceuticals containingsaid non-zero-spin nuclei that are injected and/or ingested by thepatient and then physically distributed through tissues. 15: The methodof claim 8 wherein said ablation and/or controlled heating and/oractivation of chemical reactions are intended for: a. therapy forreduction in the health/growth of sparse tumors or other undesiredtissue populating one or more regions of the body; and/or b. removal ofblood clots; and/or c. activation by controlled heating of blood vesselstents where the stent is covered by or constructed with materialsresponsive to NMR frequencies; and/or d. acceleration of attraction andblood stream absorption of undesired chemical compounds from cellshaving heavy concentrations of the undesired compounds; once in thebloodstream, their subsequent elimination from the body is achievablevia natural liver function; and/or e. acceleration of platinum-basedchemotherapy; and/or f. acceleration of cobalamin therapy in the humanbody. 16: An apparatus to perform a real-time, non-invasive, unmanned,or semi-unmanned surgical operation comprising of: a. an apparatusand/or several apparatus n4 that simultaneously transmit microwaves n7of the Larmor frequency of nuclei, with the positions controlled in realtime by mechanical support; b. a permanent magnetic field n6 with anon-uniform distribution and with mechanical and/or electronic controlof said permanent magnetic field's shape; c. a real-time, non-invasiveheating generator that generates heat, and/or accelerates a chemicalreaction, and/or performs ablation. 17: The apparatus of claim 16wherein said microwaves n7 are modulated with the Larmor frequency ofelectrons. 18: The apparatus of claim 16 wherein said real-time tissueablation is performed by non-invasive, high-intensity focusedultrasound. 19: The apparatus of claim 16 wherein said real-time tissueablation, and/or chemical reaction activation, and/or heat generation,and/or implant activation is performed on an intersection of a. saidpermanent magnetic field n6, b. said microwave beam(s) n7, and c.non-zero-spin nuclei. 20: The apparatus of claim 16 wherein saidpermanent magnetic field is made using permanent magnet(s) n1 that havenon-uniform magnetic polarization such that the magnetic strength in themeasured area is greater than the magnetic strength of an anisotropicmagnet of the same material and size.